SFN promotes renal fibrosis via binding with MYH9 in chronic kidney disease

• DOI: 10.1016/j.ejphar.2024.176806
• Publication Date: 2024-07-09T00:06:18Z
• Authors: Fang Wang; Xiao-guo Suo; Jia-nan Wang; Cheng-yi Liu; Cheng-cheng Liu; Cong Wang; Jing Li; Zi-hao Duan; Feng-sen Zhang; Yi-miao Xia; Jun-jie Jiang; Yun-wu Hao; Guang-yuan Li; Xiao-ming Meng; Yun-xia Shao; Fa-cai Wang
• Keywords: Male; Myosin Heavy Chains; Molecular Motor Proteins; Kidney; Fibrosis; Cell Line; Mice, Inbred C57BL; Transforming Growth Factor beta1; Mice; Disease Models, Animal; Animals; Humans; Renal Insufficiency, Chronic; Ureteral Obstruction; Protein Binding

Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-β1) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.