Abstract: TH-PO210
Zyxin Attenuates Hypertension-Induced Kidney Fibrosis by Modulating the CDK8-YAP Axis
Session Information
- Hypertension and CVD: Basic Research Findings
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Huang, Wei, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, China
- Zhang, Chun, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, China
Background
Hypertensive nephropathy (HN) is characterized by progressive renal tubulointerstitial fibrosis. However, the mechanisms of tubulointerstitial fibrosis in HN remains obscure. Zyxin, a focal adhesion protein, has been implicated in hypertensive myocardial fibrosis, but its role in HN remains unclear.
Methods
A hypertensive nephropathy model was established in C57BL/6 mice using subcutaneous DOCA particles and AngII pumps. Human renal tubular epithelial cells (HK-2) were stimulated with AngII in vitro. Zyxin was knocked down or overexpressed in HK-2 cells after exposure to AngII. The expression levels of zyxin, CDK8, YAP, and TRPC3 were assessed using Western blot, PCR, immunohistochemistry, and immunofluorescence.
Results
In hypertensive kidney tissues and AngII-stimulated HK-2 cells, zyxin expression was significantly downregulated, while CDK8, YAP, and TRPC3 expressions were upregulated. Overexpression of zyxin in kidney significantly ameliorated hypertensive renal fibrosis. In HK-2 cells, zyxin overexpression inhibited AngII-induced fibrosis markers, whereas zyxin knockdown promoted them. Overexpression of zyxin attenuated the increase in CDK8 and YAP, while zyxin knockdown exacerbated it. Inhibition of TRPC3 blocked the changes in zyxin, CDK8, and YAP expressions.
Conclusion
In hypertensive conditions, activated TRPC3 in the kidney inhibits zyxin expression, thereby activating the CDK8-YAP axis and promoting renal fibrosis. These findings suggest that zyxin might be a promising therapeutic target for hypertensive nephropathy.