Upregulation of Metrnl improves diabetic kidney disease by inhibiting the TGF-β1/Smads signaling pathway: A potential therapeutic target

by Lu Lin, Shulin Huang, Xin Lin, Xiaoling Liu, Xiangjin Xu, Chunmei Li, Pin Chen

This study comprises an investigation of the role of meteorin-like (Metrnl) in an experimental model of diabetic kidney disease (DKD).

Twenty-four db/db mice were randomly assigned to one of the following groups: DKD, DKD + Metrnl^-/-, and DKD + Metrnl^+/+. Plasma Metrnl concentrations were measured using ELISA. Kidney tissues were examined via western blotting, qRT-PCR, and immunohistochemistry to determine the expression levels of inflammatory factors. Electron microscopy was employed to observe stained kidney sections.

Compared with the NC group, FBG, BW, and UACR were elevated in the DKD and Metrnl^-/- groups, with severe renal pathological injury, decreased serum Metrnl concentration, decreased renal Metrnl expression, and increased expression levels of TNF-α, TGF-β1, TGF-R1, pSmad2, pSmad3, and α-SMA. In contrast, the Metrnl^+/+ group showed decreased FBG and UACR, BUN, TC and TG, increased HDL-C and serum Metrnl concentration, increased renal Metrnl expression, and decreased expression of TNF-α, TGF-β1, TGF-R1, pSmad2, pSmad3, and α-SMA, compared to the DKD and Metrnl^-/- groups. A Pearson bivariate correlation analysis revealed a negative correlation between UACR and Metrnl, and a positive correlation between UACR and TGF-β1.

Upregulation of renal Metrnl expression can improve renal injury by downregulating the expression of molecules in the TGF-β1/Smads signaling pathway in the renal tissues of type 2 diabetic mice; and by reducing the production of fibrotic molecules such as α-SMA.