慢性肾脏病(CKD)是一种以持续肾功能下降为特征的临床综合征。肾纤维化是CKD的主要病理过程,但有效的治疗方法并不存在.Stratifin(SFN)是一种高度保守的,多功能可溶性酸性蛋白。因此,本研究探讨了SFN对CKD的影响。首先,我们发现SFN在CKD患者中高表达,以及CKD动物和细胞模型。接下来,我们诱导了人肾小管上皮细胞的损伤和纤维化,SFN击倒逆转了这些影响。此外,SFN敲除减轻了输尿管梗阻(UUO)诱导的小鼠肾小管扩张和肾间质纤维化。液相色谱-串联质谱/质谱(LC-MS/MS),免疫共沉淀(Co-IP),免疫荧光共定位实验表明,SFN结合非肌肉肌球蛋白编码基因,肌球蛋白重链9(MYH9),在肾小管上皮细胞的细胞质中。MYH9敲低也降低了Col-1和α-SMA的表达,是纤维化标志物。最后,沉默SFN降低MYH9表达,减轻肾脏纤维化。这些结果表明,SFN通过与MYH9相互作用促进CKD肾脏纤维化。本研究可能为CKD的治疗提供潜在的策略。
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.