Smad2 and Smad3 play antagonistic roles in high glucose-induced renal tubular fibrosis via the regulation of SnoN.

In this study, the expression of Smad2 and Smad3 proteins, SnoN mRNA, SnoN proteins, and the ubiquitination levels of SnoN were determined in DN rats and renal tubular epithelial cells(NRK52E cells). Knockdown and overexpression of Smad2 or Smad3 in NRK52E cells were used to investigate the specific roles of Smad2 and Smad3 in the development of high glucose-induced renal tubular fibrosis, with a specific focus on their effect on the regulation of SnoN expression. Our study demonstrated that Smad3 could inhibit SnoN expression and increase ECM deposition in NRK52E cells, to promote high glucose-induced renal tubular fibrosis. In contrast, Smad2 could induce SnoN expression and reduce ECM deposition, to inhibit high glucose-induced fibrosis. The underlying mechanism involves regulation of SnoN expression. These findings provide a novel mechanism to understanding the significant role of the TGF-β1/ Smad2/3 pathway in DN.
PMID: 31917288 [PubMed - as supplied by publisher]

Source: Experimental and Molecular Pathology - January 5, 2020 Category: Pathology Authors: Wang Y, Zhang X, Mao Y, Liang L, Liu L, Peng W, Liu H, Xiao Y, Zhang Y, Zhang F, Shi M, Liu L, Guo B Tags: Exp Mol Pathol Source Type: research