Authors
Wei Huang, Yi-Yuan Chen, Yu-Mei Wang, Si-Jia Du, Yu Hao, Chun Zhang, Xiao-Li Zhang, Fang-Fang He
Published in
Inflammation research : official journal of the European Histamine Research Society ... [et al.]. Volume 75. Issue 1. Oct 17, 2026. Epub Oct 17, 2026.
Abstract
Tubulointerstitial fibrosis and inflammation are hallmark pathological features of hypertensive nephropathy (HN), yet the underlying molecular mechanisms remain elusive. Zyxin, a focal adhesion protein, has been implicated in hypertension-related pathologies, but its specific role in HN-induced tubulointerstitial injury remains undefined.
An HN murine model was established via a multi‑hit DOCA/Ang II + uninephrectomy + high salt approach. Intrarenal zyxin was overexpressed using adeno-associated virus. In vitro, HK-2 cells were stimulated with Ang II, and zyxin levels were modulated via lentiviral transduction. Renal function, inflammation, and fibrosis were evaluated through biochemical assays and molecular signaling analysis.
Zyxin was significantly downregulated in the renal tubules of HN mice and Ang II-treated HK-2 cells. Zyxin overexpression significantly improved renal function and attenuated tubulointerstitial injury, with a representative reduction of approximately 40% in the expression of fibrotic markers. These protective effects occurred independently of blood pressure changes. Mechanistically, zyxin reduction is linked to Ang II-induced calpain activation. The resulting zyxin depletion potentially disinhibits the FAK/Skp2 axis and enhances CDK8/YAP signaling, which may contribute to renal inflammation and interstitial fibrosis.
These findings support a model in which zyxin acts as a protective factor in the renal tubules during HN, suggesting its potential as a novel therapeutic target.
PMID:
42892642
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.
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