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Renal fibrosis is a progressive and chronic process that influences kidneys with chronic kidney disease (CKD), irrespective of cause, leading to irreversible failure of renal function and end-stage kidney disease. Among the signaling related to renal fibrosis, transforming growth factor-β1 (TGF-β1) signaling is a major pathway that induces the activation of myofibroblasts and the production of extracellular matrix (ECM) molecules. Apamin, a component of bee venom (BV), has been studied in relation to various diseases. However, the effect of apamin on renal interstitial fibrosis has not been investigated. The aim of this study was to estimate the beneficial effect of apamin in unilateral ureteral obstruction (UUO)-induced renal fibrosis and TGF-β1-induced renal fibroblast activation. This study revealed that obstructive kidney injury induced an inflammatory response, tubular atrophy, and ECM accumulation. However, apamin treatment suppressed the increased expression of fibrotic-related genes, including α-SMA, vimentin, and fibronectin. Administration of apamin also attenuated the renal tubular cells injury and tubular atrophy. In addition, apamin attenuated fibroblast activation, ECM synthesis, and inflammatory cytokines such as TNF-α, IL-1β, and IL-6 by suppressing the TGF-β1-canonical and non-canonical signaling pathways. This study showed that apamin inhibits UUO-induced renal fibrosis in vivo and TGF-β1-induced renal fibroblasts activation in vitro. Apamin inhibited the inflammatory response, tubular atrophy, ECM accumulation, fibroblast activation, and renal interstitial fibrosis through suppression of TGF-β1/Smad2/3 and STAT3 signaling pathways. These results suggest that apamin might be a potential therapeutic agent for renal fibrosis. UUO injury can induce renal dysfunction; however, apamin administration prevents renal failure in UUO mice. Apamin inhibited renal inflammatory response and ECM deposition in UUO-injured mice. Apamin suppressed the activation of myofibroblasts in vivo and in vitro. Apamin has the anti-fibrotic effect on renal fibrosis via regulation of TGF-β1 canonical and non-canonical signaling.
Mi-Gyeong Gwon; Hyun-Jin An; Hyemin Gu; Young-Ah Kim; Sang Mi Han; Kwan-Kyu Park. Apamin inhibits renal fibrosis via suppressing TGF-β1 and STAT3 signaling in vivo and in vitro. Journal of Molecular Medicine 2021, 99, 1265 -1277.
AMA StyleMi-Gyeong Gwon, Hyun-Jin An, Hyemin Gu, Young-Ah Kim, Sang Mi Han, Kwan-Kyu Park. Apamin inhibits renal fibrosis via suppressing TGF-β1 and STAT3 signaling in vivo and in vitro. Journal of Molecular Medicine. 2021; 99 (9):1265-1277.
Chicago/Turabian StyleMi-Gyeong Gwon; Hyun-Jin An; Hyemin Gu; Young-Ah Kim; Sang Mi Han; Kwan-Kyu Park. 2021. "Apamin inhibits renal fibrosis via suppressing TGF-β1 and STAT3 signaling in vivo and in vitro." Journal of Molecular Medicine 99, no. 9: 1265-1277.
Autophagy in the proximal tubules may promote fibrosis by activating tubular cell death, interstitial inflammation, and the production of pro-fibrotic factors. The signal transducer and activator of transcription 3 (STAT3) is activated as a potential transcription factor, which mediates the stimulation of renal fibrosis. We investigated the role of the STAT3 in autophagy and its effect on the prevention of interstitial renal fibrosis. In this study, we use synthesized STAT3 decoy oligonucleotides (ODN), which were injected into the tail veins of unilateral ureteral obstruction (UUO) mice, to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and collagen were decreased by STAT3 decoy ODN. The autophagy markers microtubule-associated protein light chain 3 (LC3) and fibronectin, were identified through immunofluorescent staining, indicating that they were reduced in the group injected with ODN. The expressions of LC3, Beclin1, p62, and autophagy-related 5–12 (Atg5–12) and hypoxia inducible factor-1α (HIF-1α) were inhibited in the ODN injection group. We determined the inhibitory effect of autophagy in chronic kidney disease and confirmed that STAT3 decoy ODN effectively inhibited autophagy by inhibiting the expression of STAT3 transcription factors in the UUO group.
Young-Ah Kim; Hyun-Ju Kim; Mi-Gyeong Gwon; Hyemin Gu; Hyun-Jin An; Seongjae Bae; Jaechan Leem; Hyun Jung; Kwan-Kyu Park. Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis. Biomedicines 2021, 9, 331 .
AMA StyleYoung-Ah Kim, Hyun-Ju Kim, Mi-Gyeong Gwon, Hyemin Gu, Hyun-Jin An, Seongjae Bae, Jaechan Leem, Hyun Jung, Kwan-Kyu Park. Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis. Biomedicines. 2021; 9 (4):331.
Chicago/Turabian StyleYoung-Ah Kim; Hyun-Ju Kim; Mi-Gyeong Gwon; Hyemin Gu; Hyun-Jin An; Seongjae Bae; Jaechan Leem; Hyun Jung; Kwan-Kyu Park. 2021. "Inhibitory Effects of STAT3 Transcription Factor by Synthetic Decoy ODNs on Autophagy in Renal Fibrosis." Biomedicines 9, no. 4: 331.
Emerging evidence suggests that epigenetic mechanisms such as histone modification are crucially involved in the pathophysiology of acute kidney injury (AKI). The histone acetyltransferase p300 regulates several biological processes through the acetylation of histones or transcription factors. However, the role of p300 in cisplatin-induced AKI remains poorly understood. Therefore, we investigated the effects of garcinol, a potent p300 inhibitor, on cisplatin-induced AKI and explored the mechanisms. Administration of garcinol significantly reversed the upregulation of p300 and increased acetylation of histone H3, along with amelioration of renal dysfunction and histopathological injury in the kidneys of cisplatin-injected mice. Garcinol also attenuated oxidative stress and reduced expression of pro-oxidant enzymes. In addition, garcinol reduced the elevated production of cytokines and chemokines and suppressed immune cell accumulation together with downregulation of vascular adhesion molecules. These beneficial effects of garcinol were associated with a reduction in acetylation of the p65 subunit of nuclear factor kappa-B. Further, garcinol significantly inhibited apoptosis and caspase-3 activation, with a decrease in p53 acetylation in cisplatin-injected mice. Taken together, we demonstrated that the inhibition of p300 by garcinol ameliorated cisplatin-induced renal injury, presumably through epigenetic mechanisms. These results suggest that garcinol might be a potential preventive agent for cisplatin-induced AKI.
Jung-Yeon Kim; Jungmin Jo; Jaechan Leem; Kwan-Kyu Park. Inhibition of p300 by Garcinol Protects against Cisplatin-Induced Acute Kidney Injury through Suppression of Oxidative Stress, Inflammation, and Tubular Cell Death in Mice. Antioxidants 2020, 9, 1271 .
AMA StyleJung-Yeon Kim, Jungmin Jo, Jaechan Leem, Kwan-Kyu Park. Inhibition of p300 by Garcinol Protects against Cisplatin-Induced Acute Kidney Injury through Suppression of Oxidative Stress, Inflammation, and Tubular Cell Death in Mice. Antioxidants. 2020; 9 (12):1271.
Chicago/Turabian StyleJung-Yeon Kim; Jungmin Jo; Jaechan Leem; Kwan-Kyu Park. 2020. "Inhibition of p300 by Garcinol Protects against Cisplatin-Induced Acute Kidney Injury through Suppression of Oxidative Stress, Inflammation, and Tubular Cell Death in Mice." Antioxidants 9, no. 12: 1271.
Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.
Jung-Yeon Kim; Jungmin Jo; Jaechan Leem; Kwan-Kyu Park. Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice. Biomedicines 2020, 8, 572 .
AMA StyleJung-Yeon Kim, Jungmin Jo, Jaechan Leem, Kwan-Kyu Park. Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice. Biomedicines. 2020; 8 (12):572.
Chicago/Turabian StyleJung-Yeon Kim; Jungmin Jo; Jaechan Leem; Kwan-Kyu Park. 2020. "Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice." Biomedicines 8, no. 12: 572.
Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.
Jung-Yeon Kim; Jaechan Leem; Kwan-Kyu Park. Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury. Molecules 2020, 25, 5717 .
AMA StyleJung-Yeon Kim, Jaechan Leem, Kwan-Kyu Park. Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury. Molecules. 2020; 25 (23):5717.
Chicago/Turabian StyleJung-Yeon Kim; Jaechan Leem; Kwan-Kyu Park. 2020. "Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury." Molecules 25, no. 23: 5717.
Background Renal fibrosis is a progressive and chronic process that influences kidneys with chronic kidney disease (CKD), irrespective of cause, leading to irreversible failure of renal function and end-stage kidney disease. Among the signaling related to renal fibrosis, transforming growth factor-β1 (TGF-β1) signaling is a major pathway that induces the activation of myofibroblasts and the production of extracellular matrix (ECM) molecules. Apamin, a component of bee venom (BV), has been studied in relation to various diseases. However, the effect of apamin on renal interstitial fibrosis has not been investigated. The aim of this study was to estimate the beneficial effect of apamin in unilateral ureteral obstruction (UUO)-induced renal fibrosis and TGF-β1-induced renal fibroblast activation.Results This study revealed that obstructive kidney injury induced an inflammatory response, tubular atrophy, and ECM accumulation. However, apamin treatment suppressed the increased expression of fibrotic-related genes, including α-SMA, vimentin, and fibronectin. Administration of apamin also attenuated the renal tubular cells injury and tubular atrophy. In addition, apamin attenuated fibroblast activation, ECM synthesis, and inflammatory cytokines such as TNF-α, IL-1β and IL-6 by suppressing the TGF-β1-canonical and non-canonical signaling pathways.Conclusions This study shown that apamin inhibites UUO-induced renal fibrosis in vivo and TGF-β1-induced renal fibroblasts activation in vitro. Apamin inhibited the inflammatory response, tubular atrophy, ECM accumulation, fibroblast activation, and renal interstitial fibrosis through suppression of TGF-β1/Smad2/3 and STAT3 signaling pathways. These results suggest that apamin might be a potential therapeutic agent for renal fibrosis.
Mi-Gyoeng Gwon; Hyun-Jin An; Hyemin Gu; Young-Ah Kim; Sang Mi Han; Kwan-Kyu Park. Apamin inhibits renal interstitial inflammation and fibrosis via suppressing TGF-β1 and STAT3 signaling pathway in vivo and in vitro. 2020, 1 .
AMA StyleMi-Gyoeng Gwon, Hyun-Jin An, Hyemin Gu, Young-Ah Kim, Sang Mi Han, Kwan-Kyu Park. Apamin inhibits renal interstitial inflammation and fibrosis via suppressing TGF-β1 and STAT3 signaling pathway in vivo and in vitro. . 2020; ():1.
Chicago/Turabian StyleMi-Gyoeng Gwon; Hyun-Jin An; Hyemin Gu; Young-Ah Kim; Sang Mi Han; Kwan-Kyu Park. 2020. "Apamin inhibits renal interstitial inflammation and fibrosis via suppressing TGF-β1 and STAT3 signaling pathway in vivo and in vitro." , no. : 1.
Jae Hoon Lee; Junmo Kim; Sun-Jae Lee; Young-Ah Kim; Young-In Maeng; Kwan-Kyu Park. Apoptosis and fibrosis of vascular smooth muscle cells in aortic dissection: an immunohistochemical study. 2020, 13, 1962 -1969.
AMA StyleJae Hoon Lee, Junmo Kim, Sun-Jae Lee, Young-Ah Kim, Young-In Maeng, Kwan-Kyu Park. Apoptosis and fibrosis of vascular smooth muscle cells in aortic dissection: an immunohistochemical study. . 2020; 13 (8):1962-1969.
Chicago/Turabian StyleJae Hoon Lee; Junmo Kim; Sun-Jae Lee; Young-Ah Kim; Young-In Maeng; Kwan-Kyu Park. 2020. "Apoptosis and fibrosis of vascular smooth muscle cells in aortic dissection: an immunohistochemical study." 13, no. 8: 1962-1969.
Sepsis-associated acute kidney injury (AKI) is a leading cause of death in hospitalized patients worldwide. Despite decades of effort, there is no effective treatment for preventing the serious medical condition. Bee venom has long been used to treat a variety of inflammatory diseases. However, whether bee venom has protective effects against lipopolysaccharide (LPS)-induced AKI has not been explored. The aim of this study was to evaluate the effects of bee venom on LPS-induced AKI. The administration of bee venom alleviated renal dysfunction and structural injury in LPS-treated mice. Increased renal levels of tubular injury markers after LPS treatment were also suppressed by bee venom. Mechanistically, bee venom significantly reduced plasma and tissue levels of inflammatory cytokines and immune cell infiltration into damaged kidneys. In addition, mice treated with bee venom exhibited reduced renal expression of lipid peroxidation markers after LPS injection. Moreover, bee venom attenuated tubular cell apoptosis in the kidneys of LPS-treated mice. In conclusion, these results suggest that bee venom attenuates LPS-induced renal dysfunction and structural injury via the suppression of inflammation, oxidative stress, and tubular cell apoptosis, and might be a useful therapeutic option for preventing endotoxemia-related AKI.
Jung-Yeon Kim; Sun-Jae Lee; Young-In Maeng; Jaechan Leem; Kwan-Kyu Park. Protective Effects of Bee Venom against Endotoxemia-Related Acute Kidney Injury in Mice. Biology 2020, 9, 154 .
AMA StyleJung-Yeon Kim, Sun-Jae Lee, Young-In Maeng, Jaechan Leem, Kwan-Kyu Park. Protective Effects of Bee Venom against Endotoxemia-Related Acute Kidney Injury in Mice. Biology. 2020; 9 (7):154.
Chicago/Turabian StyleJung-Yeon Kim; Sun-Jae Lee; Young-In Maeng; Jaechan Leem; Kwan-Kyu Park. 2020. "Protective Effects of Bee Venom against Endotoxemia-Related Acute Kidney Injury in Mice." Biology 9, no. 7: 154.
Neuroinflammation plays a vital role in neurodegenerative conditions. Microglia are a key component of the neuroinflammatory response. There is a growing interest in developing drugs to target microglia and thereby control neuroinflammatory processes. Apamin (APM) is a specifically selective antagonist of small conductance calcium-activated potassium (SK) channels. However, its effect on neuroinflammation is largely unknown. We examine the effects of APM on lipopolysaccharide (LPS)-stimulated BV2 and rat primary microglial cells. Regarding the molecular mechanism by which APM significantly inhibits proinflammatory cytokine production and microglial cell activation, we found that APM does so by reducing the expression of phosphorylated CaMKII and toll-like receptor (TLR4). In particular, APM potently suppressed the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription (STAT)3 and phosphorylated mitogen-activated protein kinases (MAPK)-extracellular signal-regulated kinase (ERK). In addition, the correlation of NF-κB/STAT3 and MAPK-ERK in the neuroinflammatory response was verified through inhibitors. The literature and our findings suggest that APM is a promising candidate for an anti-neuroinflammatory agent and can potentially be used for the prevention and treatment of various neurological disorders.
Jihyun Park; Kyung Mi Jang; Kwan-Kyu Park. Apamin Suppresses LPS-Induced Neuroinflammatory Responses by Regulating SK Channels and TLR4-Mediated Signaling Pathways. International Journal of Molecular Sciences 2020, 21, 1 .
AMA StyleJihyun Park, Kyung Mi Jang, Kwan-Kyu Park. Apamin Suppresses LPS-Induced Neuroinflammatory Responses by Regulating SK Channels and TLR4-Mediated Signaling Pathways. International Journal of Molecular Sciences. 2020; 21 (12):1.
Chicago/Turabian StyleJihyun Park; Kyung Mi Jang; Kwan-Kyu Park. 2020. "Apamin Suppresses LPS-Induced Neuroinflammatory Responses by Regulating SK Channels and TLR4-Mediated Signaling Pathways." International Journal of Molecular Sciences 21, no. 12: 1.
Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.
Young-Ah Kim; Kwan-Kyu Park; Sun-Jae Lee. LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma. International Journal of Molecular Sciences 2020, 21, 2883 .
AMA StyleYoung-Ah Kim, Kwan-Kyu Park, Sun-Jae Lee. LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2020; 21 (8):2883.
Chicago/Turabian StyleYoung-Ah Kim; Kwan-Kyu Park; Sun-Jae Lee. 2020. "LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma." International Journal of Molecular Sciences 21, no. 8: 2883.
Many studies have made clear that most of the genome is transcribed into noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), both of which can affect different cell features. LncRNAs are long heterogeneous RNAs that regulate gene expression and a variety of signaling pathways involved in cellular homeostasis and development. Several studies have demonstrated that lncRNA is an important class of regulatory molecule that can be targeted to change cellular physiology and function. The expression or dysfunction of lncRNAs is closely related to various hereditary, autoimmune, and metabolic diseases, and tumors. Specifically, recent work has shown that lncRNAs have an important role in kidney pathogenesis. The effective roles of lncRNAs have been recognized in renal ischemia, injury, inflammation, fibrosis, glomerular diseases, renal transplantation, and renal-cell carcinoma. The present review focuses on the emerging role and function of lncRNAs in the pathogenesis of kidney inflammation and fibrosis as novel essential regulators. Although lncRNAs are important players in the initiation and progression of many pathological processes, their role in renal fibrosis remains unclear. This review summarizes the current understanding of lncRNAs in the pathogenesis of kidney fibrosis and elucidates the potential role of these novel regulatory molecules as therapeutic targets for the clinical treatment of kidney inflammation and fibrosis.
Hyun Jin Jung; Hyun-Ju Kim; Kwan-Kyu Park. Potential Roles of Long Noncoding RNAs as Therapeutic Targets in Renal Fibrosis. International Journal of Molecular Sciences 2020, 21, 2698 .
AMA StyleHyun Jin Jung, Hyun-Ju Kim, Kwan-Kyu Park. Potential Roles of Long Noncoding RNAs as Therapeutic Targets in Renal Fibrosis. International Journal of Molecular Sciences. 2020; 21 (8):2698.
Chicago/Turabian StyleHyun Jin Jung; Hyun-Ju Kim; Kwan-Kyu Park. 2020. "Potential Roles of Long Noncoding RNAs as Therapeutic Targets in Renal Fibrosis." International Journal of Molecular Sciences 21, no. 8: 2698.
Bee venom is a natural toxin produced by honeybees and plays an important role in defending bee colonies. Bee venom has several kinds of peptides, including melittin, apamin, adolapamine, and mast cell degranulation peptides. Apamin accounts for about 2%–3% dry weight of bee venom and is a peptide neurotoxin that contains 18 amino acid residues that are tightly crosslinked by two disulfide bonds. It is well known for its pharmacological functions, which irreversibly block Ca2+-activated K+ (SK) channels. Apamin regulates gene expression in various signal transduction pathways involved in cell development. The aim of this study was to review the current understanding of apamin in the treatment of apoptosis, fibrosis, and central nervous system diseases, which are the pathological processes of various diseases. Apamin’s potential therapeutic and pharmacological applications are also discussed.
Hyemin Gu; Sang Mi Han; Kwan-Kyu Park. Therapeutic Effects of Apamin as a Bee Venom Component for Non-Neoplastic Disease. Toxins 2020, 12, 195 .
AMA StyleHyemin Gu, Sang Mi Han, Kwan-Kyu Park. Therapeutic Effects of Apamin as a Bee Venom Component for Non-Neoplastic Disease. Toxins. 2020; 12 (3):195.
Chicago/Turabian StyleHyemin Gu; Sang Mi Han; Kwan-Kyu Park. 2020. "Therapeutic Effects of Apamin as a Bee Venom Component for Non-Neoplastic Disease." Toxins 12, no. 3: 195.
Hyperlipidemia is a chronic disorder that plays an important role in the development of cardiovascular diseases, type II diabetes, atherosclerosis, hypertension, and non-alcoholic fatty liver disease. Hyperlipidemias have created a worldwide health crisis and impose a substantial burden not only on personal health but also on societies and economies. Transcription factors in the sterol regulatory element binding protein (SREBP) family are key regulators of the lipogenic genes in the liver. SREBPs regulate lipid homeostasis by controlling the expression of a range of enzymes required for the synthesis of endogenous cholesterol, fatty acids, triacylglycerol, and phospholipids. Thereby, SREBPs have been considered as targets for the treatment of metabolic diseases. The aim of this study was to investigate the beneficial functions and the possible underlying molecular mechanisms of SREBP decoy ODN, which is a novel inhibitor of SREBPs, in high-fat diet (HFD)-fed hyperlipidemic mice. Our studies using HFD-induced hyperlipidemia animal model revealed that SREBB decoy ODN inhibited the increased expression of fatty acid synthetic pathway, such as SREBP-1c, FAS, SCD-1, ACC1, and HMGCR. In addition, SREBP decoy ODN decreased pro-inflammatory cytokines, including TNF-α, IL-1β, IL-8, and IL-6 expression. These results suggest that SREBP decoy ODN exerts its anti-hyperlipidemia effects in HFD-induced hyperlipidemia mice by regulating their lipid metabolism and inhibiting lipogenesis through inactivation of the SREPB pathway.
Hyun-Jin An; Jung-Yeon Kim; Mi-Gyeong Gwon; Hyemin Gu; Hyun-Ju Kim; Jaechan Leem; Sung Won Youn; Kwan-Kyu Park. Beneficial Effects of SREBP Decoy Oligodeoxynucleotide in an Animal Model of Hyperlipidemia. International Journal of Molecular Sciences 2020, 21, 552 .
AMA StyleHyun-Jin An, Jung-Yeon Kim, Mi-Gyeong Gwon, Hyemin Gu, Hyun-Ju Kim, Jaechan Leem, Sung Won Youn, Kwan-Kyu Park. Beneficial Effects of SREBP Decoy Oligodeoxynucleotide in an Animal Model of Hyperlipidemia. International Journal of Molecular Sciences. 2020; 21 (2):552.
Chicago/Turabian StyleHyun-Jin An; Jung-Yeon Kim; Mi-Gyeong Gwon; Hyemin Gu; Hyun-Ju Kim; Jaechan Leem; Sung Won Youn; Kwan-Kyu Park. 2020. "Beneficial Effects of SREBP Decoy Oligodeoxynucleotide in an Animal Model of Hyperlipidemia." International Journal of Molecular Sciences 21, no. 2: 552.
Accumulating evidence suggests that the pineal hormone melatonin displays protective effects against renal fibrosis, but the mechanisms remain poorly understood. Here, we investigate the effect of the pineal hormone on transdifferentiation of renal fibroblasts to myofibroblasts invoked by transforming growth factor-β1 (TGF-β1). Increased proliferation and activation of renal interstitial fibroblasts after TGF-β1 treatment were attenuated by melatonin pretreatment. Mechanistically, melatonin suppressed Smad2/3 phosphorylation and nuclear co-localization of their phosphorylated forms and Smad4 after TGF-β1 stimulation. In addition, increased phosphorylations of Akt, extracellular signal-regulated kinase 1/2, and p38 after TGF-β1 treatment were also suppressed by the hormone. These effects of melatonin were not affected by pharmacological and genetic inhibition of its membrane receptors. Furthermore, melatonin significantly reversed an increase of intracellular reactive oxygen species (ROS) and malondialdehyde levels, and a decrease of the reduced glutathione/oxidized glutathione ratio after TGF-β1 treatment. Finally, TGF-β1-induced proliferation and activation were also suppressed by N-acetylcysteine. Altogether, these findings suggest that the pineal hormone melatonin prevents TGF-β1-induced transdifferentiation of renal interstitial fibroblasts to myofibroblasts via inhibition of Smad and non-Smad signaling cadcades by inhibiting ROS-mediated mechanisms in its receptor-independent manner.
Jung-Yeon Kim; Jae-Hyung Park; Eon Ju Jeon; Jaechan Leem; Kwan-Kyu Park; Park. Melatonin Prevents Transforming Growth Factor-β1-Stimulated Transdifferentiation of Renal Interstitial Fibroblasts to Myofibroblasts by Suppressing Reactive Oxygen Species-Dependent Mechanisms. Antioxidants 2020, 9, 39 .
AMA StyleJung-Yeon Kim, Jae-Hyung Park, Eon Ju Jeon, Jaechan Leem, Kwan-Kyu Park, Park. Melatonin Prevents Transforming Growth Factor-β1-Stimulated Transdifferentiation of Renal Interstitial Fibroblasts to Myofibroblasts by Suppressing Reactive Oxygen Species-Dependent Mechanisms. Antioxidants. 2020; 9 (1):39.
Chicago/Turabian StyleJung-Yeon Kim; Jae-Hyung Park; Eon Ju Jeon; Jaechan Leem; Kwan-Kyu Park; Park. 2020. "Melatonin Prevents Transforming Growth Factor-β1-Stimulated Transdifferentiation of Renal Interstitial Fibroblasts to Myofibroblasts by Suppressing Reactive Oxygen Species-Dependent Mechanisms." Antioxidants 9, no. 1: 39.
Background: Several studies about bee venom components have reported anti-fungal, anti-inflammatory, and anti-cancer effects. Malassezia species are components of skin flora, and also associated with many dermatologic diseases such as seborrheic dermatitis, pityriasis versicolor, folliculitis, and atopic dermatitis. Objective: To investigate the antifungal activity of bee venom components, melittin, and apamin, against Malassezia strains. Methods: With 10 Malassezia species, minimal inhibitory concentrations (MICs) were tested with bee venom, and Zinc pyrithione as a reference antifungal agent. Results: Whole bee venom, melittin, and apamin did not show any antifungal activity against Malassezia species at the concentrations tested. Conclusion: Although bee venom do not have anti-Malassezia activities, it is known to have antifungal activities against other fungal strains. Therefore, further study should consider revealing the mechanism of antifungal activity against fungus and other possible target strains of fungi.
Jin Hee Kim; Joonsoo Park; Kwan-Kyu Park; Hyun-Jin An; Yang Won Lee. Evaluation of Antifungal Activities of Bee Venom Components Against Malassezia Strains. Journal of Mycology and Infection 2019, 91 -95.
AMA StyleJin Hee Kim, Joonsoo Park, Kwan-Kyu Park, Hyun-Jin An, Yang Won Lee. Evaluation of Antifungal Activities of Bee Venom Components Against Malassezia Strains. Journal of Mycology and Infection. 2019; ():91-95.
Chicago/Turabian StyleJin Hee Kim; Joonsoo Park; Kwan-Kyu Park; Hyun-Jin An; Yang Won Lee. 2019. "Evaluation of Antifungal Activities of Bee Venom Components Against Malassezia Strains." Journal of Mycology and Infection , no. : 91-95.
Kidney fibrosis is a common process of various kidney diseases leading to end-stage renal failure irrespective of etiology. Myofibroblasts are crucial mediators in kidney fibrosis through production of extracellular matrix (ECM), but their origin has not been clearly identified. Many study proposed that epithelial and endothelial cells become myofibroblasts by epithelial dedifferentiation and endothelial-mesenchymal transition (EndoMT). TGF-β1/Smad signaling plays a crucial role in partly epithelial-mensencymal transition (EMT) and EndoMT. Thus, we designed the TGF-β1/Smad oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequence for Smad transcription factor and TGF-β1 mRNA. Therefore, this study investigated the anti-fibrotic effect of synthetic TGF-β1/Smad ODN on UUO-induced kidney fibrosis in vivo model and TGF-β1-induced in vitro model. To examine the effect of TGF-β1/Smad ODN, we performed various experiments to evaluate kidney fibrosis. The results showed that UUO induced inflammation, ECM accumulation, epithelial dedifferentiation and EndoMT processes, and tubular atrophy. However, synthetic TGF-β1/Smad ODN significantly suppressed UUO-induced fibrosis. Furthermore, synthetic ODN attenuated TGF-β1-induced epithelial dedifferentiation and EndoMT program via blocking TGF-β1/Smad signaling. In conclusion, this study demonstrated that administration of synthetic TGF-β1/Smad ODN attenuates kidney fibrosis, epithelial dedifferentiation, and EndoMT processes. The findings propose the possibility of synthetic ODN as a new effective therapeutic tool for kidney fibrosis.
Mi‐Gyeong Gwon; Hyun‐Jin An; Jung‐Yeon Kim; Woon‐Hae Kim; Hyemin Gu; Hyun‐Ju Kim; Jaechan Leem; Hyun Jin Jung; Kwan‐Kyu Park. Anti‐fibrotic effects of synthetic TGF‐β1 and Smad oligodeoxynucleotide on kidney fibrosis in vivo and in vitro through inhibition of both epithelial dedifferentiation and endothelial‐mesenchymal transitions. The FASEB Journal 2019, 34, 333 -349.
AMA StyleMi‐Gyeong Gwon, Hyun‐Jin An, Jung‐Yeon Kim, Woon‐Hae Kim, Hyemin Gu, Hyun‐Ju Kim, Jaechan Leem, Hyun Jin Jung, Kwan‐Kyu Park. Anti‐fibrotic effects of synthetic TGF‐β1 and Smad oligodeoxynucleotide on kidney fibrosis in vivo and in vitro through inhibition of both epithelial dedifferentiation and endothelial‐mesenchymal transitions. The FASEB Journal. 2019; 34 (1):333-349.
Chicago/Turabian StyleMi‐Gyeong Gwon; Hyun‐Jin An; Jung‐Yeon Kim; Woon‐Hae Kim; Hyemin Gu; Hyun‐Ju Kim; Jaechan Leem; Hyun Jin Jung; Kwan‐Kyu Park. 2019. "Anti‐fibrotic effects of synthetic TGF‐β1 and Smad oligodeoxynucleotide on kidney fibrosis in vivo and in vitro through inhibition of both epithelial dedifferentiation and endothelial‐mesenchymal transitions." The FASEB Journal 34, no. 1: 333-349.
Recent studies showed that melatonin, a well-known pineal hormone that modulates the circadian rhythm, exerts beneficial effects against liver fibrosis. However, mechanisms for its protective action against the fibrotic processes remain incompletely understood. Here, we aimed to explore the effects of the hormone on transforming growth factor-β1 (TGF-β1)-stimulated epithelial–mesenchymal transition (EMT) in AML12 hepatocytes. Pretreatment with melatonin dose-dependently reversed downregulation of an epithelial marker and upregulation of mesenchymal markers after TGF-β1 stimulation. Additionally, melatonin dose-dependently suppressed an increased phosphorylation of Smad2/3 after TGF-β1 treatment. Besides the canonical Smad signaling pathway, an increase in phosphorylation of extracellular signal-regulated kinase 1/2 and p38 was also dose-dependently attenuated by melatonin. The suppressive effect of the hormone on EMT stimulated by TGF-β1 was not affected by luzindole, an antagonist of melatonin membrane receptors, suggesting that its membrane receptors are not required for the inhibitory action of melatonin. Moreover, melatonin suppressed elevation of intracellular reactive oxygen species (ROS) levels in TGF-β1-treated cells. Finally, TGF-β1-stimulated EMT was also inhibited by the antioxidant N-acetylcysteine. Collectively, these results suggest that melatonin prevents TGF-β1-stimulated EMT through suppression of Smad and mitogen-activated protein kinase signaling cascades by deactivating ROS-dependent mechanisms in a membrane receptor-independent manner.
Jung-Yeon Kim; Jae-Hyung Park; Kiryeong Kim; Jaechan Leem; Kwan-Kyu Park; Kim; Park; Leem. Melatonin Inhibits Transforming Growth Factor-β1-Induced Epithelial–Mesenchymal Transition in AML12 Hepatocytes. Biology 2019, 8, 84 .
AMA StyleJung-Yeon Kim, Jae-Hyung Park, Kiryeong Kim, Jaechan Leem, Kwan-Kyu Park, Kim, Park, Leem. Melatonin Inhibits Transforming Growth Factor-β1-Induced Epithelial–Mesenchymal Transition in AML12 Hepatocytes. Biology. 2019; 8 (4):84.
Chicago/Turabian StyleJung-Yeon Kim; Jae-Hyung Park; Kiryeong Kim; Jaechan Leem; Kwan-Kyu Park; Kim; Park; Leem. 2019. "Melatonin Inhibits Transforming Growth Factor-β1-Induced Epithelial–Mesenchymal Transition in AML12 Hepatocytes." Biology 8, no. 4: 84.
Sirtuin 1 (Sirt1) is an essential modulator of cellular metabolism and has pleiotropic effects. It was recently reported that Sirt1 overexpression in kidney tubule ameliorates cisplatin-induced acute kidney injury (AKI). However, whether pharmacological activation of Sirt1 also has a beneficial effect against the disease remains unclear. In this study, we aimed to evaluate whether SRT1720, a potent and specific activator of Sirt1, could ameliorate cisplatin-induced AKI. We found that SRT1720 treatment ameliorated cisplatin-induced acute renal failure and histopathological alterations. Increased levels of tubular injury markers in kidneys were significantly attenuated by SRT1720. SRT1720 treatment also suppressed caspase-3 activation and apoptotic cell death. Increased expression of 4-hydroxynonenal, elevated malondialdehyde level, and decreased ratio of reduced glutathione/oxidized glutathione after cisplatin injection were significantly reversed by SRT1720. In addition, SRT1720 treatment decreased renal expression of pro-inflammatory cytokines and prevented macrophage infiltration into damaged kidneys. We also showed that the therapeutic effects of SRT1720 were associated with reduced acetylation of p53 and nuclear factor kappa-B p65 and preservation of peroxisome function, as evidenced by recovered expression of markers for number and function of peroxisome. These results suggest that Sirt1 activation by SRT1720 would be a useful therapeutic option for cisplatin-induced AKI.
Jung-Yeon Kim; Jungmin Jo; Kiryeong Kim; Hyun-Jin An; Mi-Gyeong Gwon; Hyemin Gu; Hyun-Ju Kim; A Young Yang; Sung-Woo Kim; Eon Ju Jeon; Jae-Hyung Park; Jaechan Leem; Kwan-Kyu Park. Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice. Antioxidants 2019, 8, 322 .
AMA StyleJung-Yeon Kim, Jungmin Jo, Kiryeong Kim, Hyun-Jin An, Mi-Gyeong Gwon, Hyemin Gu, Hyun-Ju Kim, A Young Yang, Sung-Woo Kim, Eon Ju Jeon, Jae-Hyung Park, Jaechan Leem, Kwan-Kyu Park. Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice. Antioxidants. 2019; 8 (8):322.
Chicago/Turabian StyleJung-Yeon Kim; Jungmin Jo; Kiryeong Kim; Hyun-Jin An; Mi-Gyeong Gwon; Hyemin Gu; Hyun-Ju Kim; A Young Yang; Sung-Woo Kim; Eon Ju Jeon; Jae-Hyung Park; Jaechan Leem; Kwan-Kyu Park. 2019. "Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice." Antioxidants 8, no. 8: 322.
Porphyromonas gingivalis (P. gingivalis) is one of the major periodontal pathogens leading to inflammation and alveolar bone resorption. Bone resorption is induced by osteoclasts, which are multinucleated giant cells. Osteoclastic bone resorption is mediated by enhanced receptor activator of nuclear factor-kappa B ligand (RANKL) signaling. Therefore, the down-regulation of RANKL downstream signals is regarded as an effective therapeutic target in the treatment of bone loss-associated disorders. The aim of this study was to evaluate whether purified bee venom (BV) could attenuate P. gingivalis-induced inflammatory periodontitis and RANKL-induced osteoclast differentiation. Inflammatory periodontitis induced by P. gingivalis increased alveolar bone resorption and increased expression of TNF-α and IL-1β, while BV treatment resulted in decreased bone loss and pro-inflammatory cytokines. Similarly, RANKL-induced multinucleated osteoclast differentiation and osteoclast-specific gene expression, such as nuclear factor of activated T cells 1 (NFATc1), cathepsin K, tartrate-resistant acid phosphatase (TRAP), and integrin αvβ3 were significantly suppressed by treatment with BV. We show that BV reduces P. gingivalis-induced inflammatory bone loss-related periodontitis in vivo and RANKL-induced osteoclast differentiation, activation, and function in vitro. These results suggest that BV exerts positive effects on inflammatory periodontitis associated osteoclastogenesis.
Hyemin Gu; Hyun-Jin An; Jung-Yeon Kim; Woon-Hae Kim; Mi-Gyeong Gwon; Hyun-Ju Kim; Sang Mi Han; Insook Park; Sok Cheon Park; Jaechan Leem; Kwan-Kyu Park. Bee venom attenuates Porphyromonas gingivalis and RANKL-induced bone resorption with osteoclastogenic differentiation. Food and Chemical Toxicology 2019, 129, 344 -353.
AMA StyleHyemin Gu, Hyun-Jin An, Jung-Yeon Kim, Woon-Hae Kim, Mi-Gyeong Gwon, Hyun-Ju Kim, Sang Mi Han, Insook Park, Sok Cheon Park, Jaechan Leem, Kwan-Kyu Park. Bee venom attenuates Porphyromonas gingivalis and RANKL-induced bone resorption with osteoclastogenic differentiation. Food and Chemical Toxicology. 2019; 129 ():344-353.
Chicago/Turabian StyleHyemin Gu; Hyun-Jin An; Jung-Yeon Kim; Woon-Hae Kim; Mi-Gyeong Gwon; Hyun-Ju Kim; Sang Mi Han; Insook Park; Sok Cheon Park; Jaechan Leem; Kwan-Kyu Park. 2019. "Bee venom attenuates Porphyromonas gingivalis and RANKL-induced bone resorption with osteoclastogenic differentiation." Food and Chemical Toxicology 129, no. : 344-353.
Caspase-1 is a proinflammatory caspase responsible for the proteolytic conversion of the precursor forms of interleukin-1β to its active form and plays an important role in the pathogenesis of various inflammatory diseases. It was reported that genetic deficiency of caspase-1 prevented cisplatin-induced nephrotoxicity. However, whether pharmacological inhibition of caspase-1 also has a preventive effect against cisplatin-induced kidney injury has not been evaluated. In this study, we examined the effect of Ac-YVAD-cmk, a potent caspase-1-specific inhibitor, on renal function and histology in cisplatin-treated mice and explored its underlying mechanisms. We found that administration of Ac-YVAD-cmk effectively attenuated cisplatin-induced renal dysfunction, as evidenced by reduced plasma levels of blood urea nitrogen and creatinine, and histological abnormalities, such as tubular cell death, dilatation, and cast formation. Administration of Ac-YVAD-cmk inhibited caspase-3 activation as well as caspase-1 activation and attenuated apoptotic cell death, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, in the kidneys of cisplatin-treated mice. Cisplatin-induced G2/M arrest of renal tubular cells was also reduced by caspase-1 inhibition. In addition, administration of Ac-YVAD-cmk reversed increased oxidative stress and depleted antioxidant capacity after cisplatin treatment. Moreover, increased macrophage accumulation and elevated expression of cytokines and chemokines were attenuated by caspase-1 inhibition. Taken together, these results suggest that caspase-1 inhibition by Ac-YVAD-cmk protects against cisplatin-induced nephrotoxicity through inhibition of renal tubular cell apoptosis, oxidative stress, and inflammatory responses. Our findings support the idea that caspase-1 may be a promising pharmacological target for the prevention of cisplatin-induced kidney injury.
Jung-Yeon Kim; Jae-Hyung Park; Kiryeong Kim; Jungmin Jo; Jaechan Leem; Kwan-Kyu Park. Pharmacological Inhibition of Caspase-1 Ameliorates Cisplatin-Induced Nephrotoxicity through Suppression of Apoptosis, Oxidative Stress, and Inflammation in Mice. Mediators of Inflammation 2018, 2018, 1 -10.
AMA StyleJung-Yeon Kim, Jae-Hyung Park, Kiryeong Kim, Jungmin Jo, Jaechan Leem, Kwan-Kyu Park. Pharmacological Inhibition of Caspase-1 Ameliorates Cisplatin-Induced Nephrotoxicity through Suppression of Apoptosis, Oxidative Stress, and Inflammation in Mice. Mediators of Inflammation. 2018; 2018 ():1-10.
Chicago/Turabian StyleJung-Yeon Kim; Jae-Hyung Park; Kiryeong Kim; Jungmin Jo; Jaechan Leem; Kwan-Kyu Park. 2018. "Pharmacological Inhibition of Caspase-1 Ameliorates Cisplatin-Induced Nephrotoxicity through Suppression of Apoptosis, Oxidative Stress, and Inflammation in Mice." Mediators of Inflammation 2018, no. : 1-10.