Circ_0000524/miR-500a-5p/CXCL16 axis promotes podocyte apoptosis in membranous nephropathy.

Podocytes apoptosis is a hallmark of membranous nephropathy (MN). Circ_0000524 has been reported to be associated with patients with MN, whereas the effect of circ_0000524 on podocytes apoptosis and the underlying mechanisms in MN have not been elaborated. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the expressions of circ_0000524, microRNA-500a-5p (miR-500a-5p), and C-X-C chemokine ligand 16 (CXCL16) in MN tissues and podocytes. Podocyte injury was induced by angiotensin II (AngII). Cell apoptosis was detected by flow cytometry. Caspase-3 or caspase-9 activity was evaluated using a caspase-3 or caspase-9 activity assay kit, respectively. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assay were used to address the relationship among circ_0000524,miR-500a-5p and CXCL16. Upregulation of circ_0000524 and CXCL16 and low expression of miR-500a-5p were observed in MN tissues. AngII treatment induced the overexpression of circ_0000524 and CXCL16, a decrease of miR-500a-5p, and induced cell apoptosis in podocytes. Circ_0000524 negatively modulated the expression of miR-500a-5p. Circ_0000524 depletion inhibited podocyte apoptosis, which was rescued by loss of miR-500a-5p. miR-500a-5p contained the binding sites with CXCL16. Circ_0000524 knockdown hampered CXCL16 expression by upregulating miR-500a-5p expression. Additionally, miR-500a-5p upregulation suppressed AngII-induced podocyte apoptosis, which was rescued by enhanced expression of CXCL16. Circ_0000524/miR-500a-5p/CXCL16 pathway regulated podocyte apoptosis in MN.

Sun Z ，Xu Q ，Ma Y ，Yang S ，Shi J ... -  《-》

Knockdown of circ_CDYL Contributes to Inhibit Angiotensin II-Induced Podocytes Apoptosis in Membranous Nephropathy via the miR-149-5p/TNFSF11 Pathway.

Circular RNAs (circRNAs) have been verified as vital regulators in various diseases, including membranous nephropathy (MN). Therefore, the role of circ_CDYL in podocyte apoptosis and MN was investigated. The real-time quantitative polymerase chain reaction was performed to measure the expression of circ_CDYL, microRNA-149-5p (miR-149-5p), and tumor necrosis factor superfamily member 11 (TNFSF11) in podocytes. In addition, angiotensin II (Ang II) was used to induce apoptosis of podocytes. The apoptosis-related protein expression was quantified by western blot assay. The apoptosis of podocytes was evaluated by flow cytometry assay. The interaction relationship between miR-149-5p and circ_CDYL or TNFSF11 was confirmed by dual-luciferase reporter assay. Circ_CDYL was significantly overexpressed in MN patients and Ang II-induced podocytes compared with control groups. Importantly, loss-of-functional experiments indicated that knockdown of circ_CDYL protected podocytes from Ang II-induced apoptosis. MiR-149-5p was verified as target of circ_CDYL and negatively correlated with circ_CDYL expression in MN patients. Knockdown of circ_CDYL-mediated effects on Ang II-induced podocyte cells were abolished by silencing miR-149-5p. Besides, the upregulation of miR-149-5p could suppress apoptosis in Ang II-induced podocyte cells by targeting TNFSF11. Under Ang II stimulation, the upregulation of TNFSF11 could increase the expression of TNFSF11 and induce apoptosis in circ_CDYL-silencing podocytes. Our results confirmed that circ_CDYL specifically targeted miR-149-5p/TNFSF11 pathway to regulate Ang II-induced apoptosis in podocytes, which might be useful diagnostic biomarkers in MN.

Qiu D ，Zhao N ，Chen Q ，Wang M ... -  《-》

MiR-130a-5p prevents angiotensin II-induced podocyte apoptosis by modulating M-type phospholipase A2 receptor.

Liu D ，Liu F ，Wang X ，Qiao Y ，Pan S ，Yang Y ，Hu Y ，Zhang Y ，Tian F ，Liu Z ... -  《-》

Down-regulation of the long non-coding RNA XIST ameliorates podocyte apoptosis in membranous nephropathy via the miR-217-TLR4 pathway.

What is the central question of this study? What is the role of the long non-coding RNA X-inactive specific transcript (XIST), which is up-regulated in injured podocytes and membranous nephropathy, in the pathogenesis of membranous nephropathy? What is the main finding and its importance? XIST was up-regulated in kidney tissue with membranous nephropathy and in injured podocytes. Down-regulation of XIST inhibited podocyte apoptosis. XIST negatively regulated miR-217, and miR-217 modulated Toll-like receptor 4. Inhibition of XIST suppressed podocyte apoptosis induced by angiotensin II via miR-217. Membranous nephropathy is often characterized by glomerular podocyte injury. Up-regulation of the long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) has been verified in membranous nephropathy and in injured podocytes. Here the role of XIST in podocyte injury and membranous nephropathy was explored. Quantitative real-time PCR and western blot were performed to detect the expression of XIST and miR-217, and Toll-like receptor 4 (TLR4) protein, respectively. Podocyte apoptosis was evaluated with flow cytometry. Interaction between XIST and miR-217 was analysed by RNA immunoprecipitation and RNA pull-down assay. A dual luciferase reporter assay was used to examine the interplay between miR-217 and TLR4. Up-regulation of the lncRNA XIST and angiotensin II (Ang II) and kidney and podocyte injury were indicated in kidney tissue of patients with membranous nephropathy. Increase of XIST and apoptosis were induced by Ang II in podocytes. Down-regulation of XIST reversed podocyte apoptosis induced by Ang II. MiR-217 was negatively regulated by XIST. MiR-217 controlled TLR4 by targeting its 3'-untranslated region. XIST modulated TLR4 through miR-217 and inhibition of XIST reduced podocyte apoptosis induced by Ang II via regulating miR-217. Down-regulation of XIST ameliorates podocyte apoptosis via the miR-217-TLR4 pathway, which may improve membranous nephropathy.

Jin LW ，Pan M ，Ye HY ，Zheng Y ，Chen Y ，Huang WW ，Xu XY ，Zheng SB ... -  《-》

Hsa_circ_0037128 aggravates high glucose-induced podocytes injury in diabetic nephropathy through mediating miR-31-5p/KLF9.

Fang R ，Cao X ，Zhu Y ，Chen Q ... -  《-》