Chronic kidney disease (CKD) is a global health problem characterized by progressive kidney failure due to uremic toxicity and the complications that arise from it. Anemia consecutive to CKD is one of its most common complications affecting nearly all patients with end-stage renal disease. Anemia is a potential cause of cardiovascular disease, faster deterioration of renal failure and mortality. Erythropoietin (produced by the kidney) and iron (provided from recycled senescent red cells) deficiencies are the main reasons that contribute to CKD-associated anemia. Indeed, accumulation of uremic toxins in blood impairs erythropoietin synthesis, compromising the growth and differentiation of red blood cells in the bone marrow, leading to a subsequent impairment of erythropoiesis. In this review, we mainly focus on the most representative uremic toxins and their effects on the molecular mechanisms underlying anemia of CKD that have been studied so far. Understanding molecular mechanisms leading to anemia due to uremic toxins could lead to the development of new treatments that will specifically target the pathophysiologic processes of anemia consecutive to CKD, such as the newly marketed erythropoiesis-stimulating agents.

TRIpartite motif (TRIM) proteins are part of the largest subfamilies of E3 ligases that mediate the transfer of ubiquitin to substrate target proteins. In this review, we focus on TRIM37 in the normal cell and in pathological conditions, with an emphasis on the MULIBREY (MUscle-LIver-BRain-EYe) genetic disorder caused by TRIM37 mutations. TRIM37 is characterized by the presence of a RING domain, B-box motifs, and a coiled-coil region, and its C-terminal part includes the MATH domain specific to TRIM37. MULIBREY nanism is a rare autosomal recessive caused by TRIM37 mutations and characterized by severe pre- and postnatal growth failure. Constrictive pericarditis is the most serious anomaly of the disease and is present in about 20% of patients. The patients have a deregulation of glucose and lipid metabolism, including type 2 diabetes, fatty liver, and hypertension. Puzzlingly, MULIBREY patients, deficient for TRIM37, are plagued with numerous tumors. Among non-MULIBREY patients affected by cancer, a wide variety of cancers are associated with an overexpression of TRIM37. This suggests that normal cells need an optimal equilibrium in TRIM37 expression. Finding a way to keep that balance could lead to potential innovative drugs for MULIBREY nanism, including heart condition and carcinogenesis treatment.

Recent progress in genomic research has highlighted the genome to be much more transcribed than expected. The formerly so-called junk DNA encodes a miscellaneous group of largely unknown RNA transcripts, which contain the long non-coding RNAs (lncRNAs) family. lncRNAs are instrumental in gene regulation. Moreover, understanding their biological roles in the physiopathology of many diseases, including renal, is a new challenge. lncRNAs regulate the effects of microRNAs (miRNA) on mRNA expression. Understanding the complex crosstalk between lncRNA–miRNA–mRNA is one of the main challenges of modern molecular biology. This review aims to summarize the role of lncRNA on kidney diseases, the molecular mechanisms involved, and their function as emerging prognostic biomarkers for both acute and chronic kidney diseases. Finally, we will also outline new therapeutic opportunities to diminish renal injury by targeting lncRNA with antisense oligonucleotides.

Morphology and changes in gene expression of vascular endothelium are mainly due to shear stress and inflammation. Cell phenotype modulation has been clearly demonstrated to be controlled by small noncoding micro-RNAs (miRNAs). This study focused on the effect of laminar shear stress (LSS) on human endothelial cells (HUVECs), with an emphasis on the role of miRNA-126 (miR-126). Exposure of HUVECsin vitroto LSS modified the shape of HUVECs and concomitantly regulated the expression of miR-126, vascular cell adhesion molecule 1 (VCAM-1), and syndecan-4 (SDC-4). A significant upregulation of miR-126 during long-term exposure to flow was shown. Interestingly, LSS enhanced SDC-4 expression on the HUVEC membranes. Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4. No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs. In Apo-E KO/CKD mice aortas expressing a high level of miR-126, SDC-4 was concomitantly increased. In conclusion, our results suggest that miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4 expression.

The aim of the present review is to synthesise and summarise our recent knowledge on the involvement of cholecystokinin (CCK) and gastrin peptides and their receptors in the control of digestive functions and more generally their role in the field of nutrition in mammals. First, we examined the release of these peptides from the gut, focusing on their molecular forms, the factors regulating their release and the signalling pathways mediating their effects. Second, general physiological effects of CCK and gastrin peptides are described with regard to their specific receptors and the role of CCK on vagal mucosal afferent nerve activities. Local effects of CCK and gastrin in the gut are also reported, including gut development, gastrointestinal motility and control of pancreatic functions through vagal afferent pathways, including NO. Third, some examples of the intervention of the CCK and gastrin peptides are exposed in diseases, taking into account intervention of the classical receptor subtypes (CCK₁and CCK₂receptors) and their heterodimerisation as well as CCK-C receptor subtype. Finally, applications and future challenges are suggested in the nutritional field (performances) and in therapy with regards to the molecular forms or in relation with the type of receptor as well as new techniques to be utilised in detection or in therapy of disease. In conclusion, the present review underlines recent developments in this field: CCK and gastrin peptides and their receptors are the key factor of nutritional aspects; a better understanding of the mechanisms involved may increase the efficiency of the nutritional functions and the treatment of abnormalities under pathological conditions.

Atherosclerosis, in the ultimate stage of cardiovascular diseases, causes an obstruction of vessels leading to ischemia and finally to necrosis. To restore vascularization and tissue regeneration, stimulation of angiogenesis is necessary. Chemokines and microRNAs (miR) were studied as pro‐angiogenic agents. We analysed the miR‐126/CXCL12 axis and compared impacts of both miR‐126‐3p and miR‐126‐5p strands effects in CXCL12‐induced angiogenesis. Indeed, the two strands of miR‐126 were previously shown to be active but were never compared together in the same experimental conditions regarding their differential functions in angiogenesis. In this study, we analysed the 2D‐angiogenesis and the migration assays in HUVEC in vitro and in rat's aortic rings ex vivo, both transfected with premiR‐126‐3p/‐5p or antimiR‐126‐3p/‐5p strands and stimulated with CXCL12. First, we showed that CXCL12 had pro‐angiogenic effects in vitro and ex vivo associated with overexpression of miR‐126‐3p in HUVEC and rat's aortas. Second, we showed that 2D‐angiogenesis and migration induced by CXCL12 was abolished in vitro and ex vivo after miR‐126‐3p inhibition. Finally, we observed that SPRED‐1 (one of miR‐126‐3p targets) was inhibited after CXCL12 treatment in HUVEC leading to improvement of CXCL12 pro‐angiogenic potential in vitro. Our results proved for the first time: 1‐the role of CXCL12 in modulation of miR‐126 expression; 2‐the involvement of miR‐126 in CXCL12 pro‐angiogenic effects; 3‐the involvement of SPRED‐1 in angiogenesis induced by miR‐126/CXCL12 axis.