Autophagy regulates cellular turnover by disassembling unnecessary or dysfunctional constituents. Recent studies demonstrated that autophagy and its regulators play a wide variety of roles in melanocyte biology. Activation of autophagy is known to induce melanogenesis and regulate melanosome biogenesis in melanocytes. Also, autophagy induction was reported to regulate physiologic skin color via melanosome degradation, although the downstream effectors are not yet clarified. To determine the role of autophagy as a melanosome degradation machinery, we administered several autophagy inducers in human keratinocytes and melanocytes. Our results showed that the synthetic autophagy inducer PTPD‐12 stimulated autophagic flux in human melanocytes and in keratinocytes containing transferred melanosomes. Increased autophagic flux led to melanosome degradation without affecting the expression of MITF. Furthermore, the color of cell pellets of both melanocytes and keratinocytes was visibly lightened. Inhibition of autophagic flux by chloroquine resulted in marked attenuation of PTPD‐12‐induced melanosome degradation, whereas the expression of melanogenesis pathway genes and proteins remained unaffected. Taken together, our results suggest that the modulation of autophagy can contribute to the regulation of melanocyte biology and skin pigmentation.

BACKGROUND: Owing to its potentially greater mechanical force on the implanted tissue, barbed thread is frequently used in face-lifting procedures. However, the long-term durability thereof remains controversial. Moreover, reports on underlying histologic and molecular changes resulting from face-lifting procedures are scarce. OBJECTIVE: To evaluate histologic and molecular changes induced by absorbable, barbed face-lifting thread in an animal model. MATERIALS AND METHODS: Fragments of monofilament, monodirectionally barbed polydioxanone thread were implanted in dorsal skin from 12 guinea pigs. Tissue samples were harvested at 1, 3, and 7 months thereafter. Histopathologic analysis and quantification of Type 1 collagen and transforming growth factor beta 1 (TGF-β1) levels were performed. RESULTS: Implantation of a single fragment induced fibrous capsule around the thread. Tissue reactions were strongest at 1 month after implantation, showing marked infiltration of inflammatory cells and fibroblasts, which gradually decreased. On molecular analysis, Type 1 collagen and TGF-β1 levels were significantly increased, compared to normal skin, throughout the 7-month study period. CONCLUSION: Our results suggest that implantation of barbed thread induces strong anchorage to skin tissue. Quantitative analysis of collagen and its downstream signaling molecule TGF-β supports the long-term durability of the thread. Therefore, the authors expect potential beneficial effect for rejuvenation on its clinical application.

Keloid scarring is a fibroproliferative disease caused by aberrant genetic activation with an unclear underlying mechanism. Genetic predisposition, aberrant cellular responses to environmental factors, increased inflammatory cytokines and epithelial–mesenchymal transition (EMT) phenomena are known as major contributors. In this study, we aimed to identify the molecular drivers that initiate keloid pathogenesis. Bulk tissue RNA sequencing analyses of keloid and normal tissues along with ex vivo and in vitro tests were performed to identify the contributing genes to keloid pathogenesis. An animal model of inflammatory keloid scarring was reproduced by replication of a skin fibrosis model with intradermal bleomycin injection in C57BL/6 mice. Gene set enrichment analysis revealed upregulation of Wnt family member 5A (WNT5A) expression and genes associated with EMT in keloid tissues. Consistently, human keloid tissues and the bleomycin-induced skin fibrosis animal model showed significantly increased expression of WNT5A and EMT markers. Increased activation of the interleukin (IL)-6/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and subsequent elevation of EMT markers was also observed in keratinocytes co-cultured with WNT5A-activated fibroblasts or keloid fibroblasts. Furthermore, WNT5A silencing and the blockage of IL-6 secretion via neutralizing IL-6 antibody reversed hyperactivation of the STAT pathway and EMT markers in keratinocytes. Lastly, STAT3 silencing significantly reduced the EMT-like phenotypes in both keratinocytes and IL-6-stimulated keratinocytes. Intercellular communication via the WNT5A and STAT pathways possibly underlies a partial mechanism of EMT-like phenomena in keloid pathogenesis. IL-6 secreted from WNT5A-activated fibroblasts or keloid fibroblasts activates the JAK/STAT signaling pathway in adjacent keratinocytes which in turn express EMT markers. A better understanding of keloid development and the role of WNT5A in EMT will promote the development of next-generation targeted treatments for keloid scars.

BACKGROUND: Recent advances in keloid management favor the administration of combination therapy over monotherapy. OBJECTIVE: The authors evaluated the safety and efficacy of combination therapy to treat keloids using fractional lasers, cryotherapy, and intralesional corticosteroids. MATERIALS AND METHODS: The authors performed a retrospective study involving 35 Korean patients. Each patient underwent treatment using the 1,550 nm nonablative fractional erbium-glass laser, followed by the 10,600 nm ablative fractional carbon dioxide laser. Laser treatment was immediately followed by the administration of superficial cryotherapy and intralesional triamcinolone injection. Therapeutic efficacy was assessed using the Vancouver Scar Scale (VSS) score and the 7-point patient self-assessment score. RESULTS: The mean total and subcategory VSS scores showed statistically significant improvements. The height and pliability scores showed the most significant and quickest responses to the combination therapy. The patients reported remarkable improvement in itching, pain, and limitations of motion after a single combination therapy session. Twenty patients were followed up for 1 year after the discontinuation of the combination treatment, and the recurrence was observed only in one patient. No significant adverse effects were observed throughout the follow-up period. CONCLUSION: Combination keloid therapy using fractional lasers, superficial cryotherapy, and intralesional triamcinolone injection is safe and more effective than individual monotherapies.

Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1) in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA) showed an opposing effect on both activities. To analyze the downstream mechanism, the protein levels of extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-κB compared to the control, which was suppressed by GA. HMGB1 promoted both normal and keloid fibroblasts migration to a degree equivalent to that achieved with TGF-β. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE)—mitogen-activated protein kinases (MAPK) and NF-κB interaction signaling pathways. Further knowledge of the relationship of HMGB1 with skin fibrosis may lead to a promising clinical approach to manage abnormal scarring.