Lncrna snhg16 aggravates high glucose-induced podocytes injury in diabetic nephropathy through targeting mir-106a and thereby up-regulating klf9

Abstract

Introduction: Diabetic nephropathy (DN) is one of the major complications of diabetes and podocyte injury plays an important role in the DN pathogenesis. MicroRNA (miR)-106a is predicated to be a target of long noncoding RNA (lncRNA) SNHG16 and has been identified as a therapeutic biomarker for diabetic kidney diseases. However, the role of SNHG16/miR-106a axis in DN has not been illustrated. This study aimed to investigate whether SNHG16 could regulate podocyte injury via miR-106a in DN and uncover the underlying mechanism. Methods: MPC5 podocytes were treated with control or high glucose (HG) medium, and then miR-106a level was measured. MPC5 cells that exposed to HG were overexpressed with miR-106a or not, following by overexpression with or without KLF9 or SNHG16. Then, cell viability, apoptosis, reactive oxygen species and the protein expression of synaptopodin and podocin were evaluated. Results: MiR-106a was down-regulated in the serum of DN patients and HG-induced MPC5 podocytes. Overexpression of miR-106a suppressed HG-induced decrease in cell viability, Bcl-2, synaptopodin and podocin expression, increase in ROS, apoptotic cells, Bax and cleaved-caspase 3 expression. MiR-106a could bind to both KLF9 and lncRNA SNHG16, which were up-regulated in the serum of DN patients and HG-induced MPC5 podocytes. The level of miR-106a was decreased by SNHG16 overexpression and miR-106a overexpression reduced KLF9 expression. Furthermore, overexpression of KLF9 or SNHG16 blunted the protective effects of miR-106a on HG-induced MPC5 injury. Discussion: LncRNA SNHG16 could promote HG-stimulated podocytes injury via targeting miR-106a to enhance KLF9 expression. The intervention of SNHG16/miR-106a/KLF9 may be a therapeutic treatment for DN.