Down‐regulation of lncRNA XIST ameliorates podocytes apoptosis in membranous nephropathy via miR‐217/TLR4 pathway

New Findings

What is the central question of this study?

Up‐regulation of lncRNA XIST in injured podocytes and membranous nephropathy has been noted, but its implication in membranous nephropathy pathogenesis has not been elucidated in detail.

What is the main finding and its importance?

We demonstrated that XIST was up‐regulated in kidney tissue of membranous nephropathy and in injured podocytes. Down‐regulation of XIST inhibited podocytes apoptosis. XIST negatively regulated miR‐217, and miR‐217 controlled TLR4. XIST modulated TLR4 through miR‐217 and inhibition of XIST suppressed podocytes apoptosis induced by Angiotensin II via miR‐217.

Abstract

Background

Membranous nephropathy is often characterized by glomerular podocyte injury. Up‐regulation of lncRNA XIST has been verified in membranous nephropathy and in injured podocytes; hence the role of XIST in podocyte injury and membranous nephropathy was explored.

Methods

QRT‐PCR and western blot were performed to detect the expression XIST, miR‐217, and TLR4 protein respectively. Podocyte apoptosis was evaluated with flow cytometry. Interaction between XIST and miR‐217 was analyzed by RIP and RNA pull‐down assay, respectively. Dual luciferase reporter assay was used to exam the interplay between miR‐217 and TLR4.

Results

LncRNA XIST and Ang II up‐regulation, 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 inverted podocytes apoptosis induced by Ang II. MiR‐217 was negatively regulated by XIST. MiR‐217 controlled TLR4 by targeting its 3′‐UTR. XIST modulated TLR4 through miR‐217 and inhibition of XIST inverted podocytes apoptosis induced by Ang II via regulating miR‐217.

Conclusion

Down‐regulation of XIST ameliorates podocytes apoptosis via the miR‐217/TLR4 pathway, which may improve membranous nephropathy.

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