1. Academic Validation
  2. Identification of YAP1 as a novel downstream effector of the FGF2/STAT3 pathway in the pathogenesis of renal tubulointerstitial fibrosis

Identification of YAP1 as a novel downstream effector of the FGF2/STAT3 pathway in the pathogenesis of renal tubulointerstitial fibrosis

  • J Cell Physiol. 2021 Nov;236(11):7655-7671. doi: 10.1002/jcp.30415.
Xiaoying Li 1 2 3 Fan Zhang 1 2 Lingling Qu 1 Ying Xie 1 Yuanyuan Ruan 1 Ziwei Guo 4 Yanwen Mao 1 Qin Zou 1 Mingjun Shi 1 2 Ying Xiao 1 2 Yuanyuan Wang 1 2 Yuxia Zhou 1 2 Bing Guo 1 2
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Guizhou Medical University, Guiyang, China.
  • 2 Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, China.
  • 3 Department of Nephrology, Guiyang First People's Hospital, Guiyang, China.
  • 4 Department of Nephrology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Abstract

Chronic kidney disease is a global health problem and eventually develops into an end-stage renal disease (ESRD). It is now widely believed that renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of ESRD. Renal tubular epithelial-mesenchymal transition (EMT) is an important cause of TIF. Studies have shown that FGF2 is highly expressed in fibrotic renal tissue, although the mechanism remains unclear. We found that FGF2 can activate STAT3 and induce EMT in renal tubular epithelial cells. STAT3, an important transcription factor, was predicted by the JASPAR biological database to bind to the promoter region of YAP1. In this study, STAT3 was shown to promote the expression of the downstream target gene YAP1 through transcription, promote EMT of renal tubular epithelial cells, and mediate the occurrence of renal TIF. This study provides a theoretical basis for the involvement of the FGF2/STAT3/YAP1 signaling pathway in the process of renal interstitial fibrosis and provides a potential target for the treatment of renal fibrosis.

Keywords

Yes-associated protein 1 (YAP1); epithelial-mesenchymal transition (EMT); fibroblast growth factor 2 (FGF2); renal tubulointerstitial fibrosis (TIF); signal transducer and activator of transcription 3 (STAT3).

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