1. HIF‐1α and adaptor protein LIM and senescent cell antigen‐like domains protein 1 axis promotes tubulointerstitial fibrosis by interacting with vimentin in angiotensin II‐induced hypertension.
- Author
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Ni, Wei‐Jie, Li, Zuo‐Lin, Wen, Xian‐Li, Ji, Jia‐Ling, Liu, Hong, Yin, Qing, Jiang, Liang‐Yun‐Zi, Zhang, Yi‐Lin, Wen, Yi, Tang, Tao‐Tao, Jiang, Wei, Lv, Lin‐Li, Gan, Wei‐Hua, Liu, Bi‐Cheng, and Wang, Bin
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RENAL fibrosis , *PROTEIN domains , *CHRONIC kidney failure , *ADAPTOR proteins , *KNOCKOUT mice , *ANGIOTENSIN II - Abstract
Background and Purpose: Activation of the renin‐angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen‐like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)‐induced hypertension and tubulointerstitial fibrosis was investigated. Experimental Approach: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) renal tubular‐specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II‐induced renal interstitial fibrosis. In vitro, HIF‐1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. Key Results: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II‐induced hypertension model. Tubular‐specific knockdown of LIMS1 ameliorated Ang II‐induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF‐1α in tubular cells and that tubular HIF‐1α knockout ameliorates LIMS1‐mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II‐induced tubulointerstitial fibrosis by interacting with vimentin. Conclusion and Implications: We conclude that HIF‐1α transcriptionally regulated LIMS1 plays a central role in Ang II‐induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II‐induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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