--- - |2- Abstract We aim to explore the relationship between Gm6135 and diabetic nephropathy. We detected the relative expression levels of Gm6135 and toll‐like receptor 4 (TLR4) in diabetic nephropathy mice and high‐glucose‐cultured mouse mesangial cells SV40‐MES‐13 by the quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blot detection. Cell proliferation and apoptosis were detected after small interfering RNA (siRNA) interference or plasmid overexpression of Gm6135/TLR4, and bioinformatics method was used to predict and screen miR‐203 as an intermediate factor. Through dual‐luciferase reporter gene, RNA pull‐down, qRT‐PCR, and western blot, the binding relationship between Gm6135, miR‐203‐3p, and TLR4 was confirmed. The possibility of the competing endogenous RNA mechanism was demonstrated by cell localization assays and rip assays. Finally, the proliferation of mouse mesangial cells SV40‐MES‐13 was detected after mimics and inhibitor of microRNA, which were reversed with TLR4 overexpression and siRNA. The results showed that the relative expression levels of Gm6135 and TLR4 in the kidney and high‐glucose‐cultured mouse mesangial cells of diabetic nephropathy mice increased significantly. Overexpression or downregulation of Gm6135/TLR4 significantly affected the proliferation and apoptosis of mouse mesangial cells. Gm6135 upregulates TLR4 by competitively binding to miR‐203‐3p. - Journal of Cellular Physiology, EarlyView.