Inhibition of STAT3 by S3I-201 suppress peritoneal fibroblast phenotype conversion and alleviate peritoneal fibrosis.

Autor: Song Q; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China., Li H; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China., Yan H; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China., Yu Z; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China., Li Z; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China., Yuan J; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China., Jiang N; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China., Ni Z; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China., Gu L; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China., Fang W; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.; Shanghai Center for Peritoneal Dialysis Research, Shanghai, People's Republic of China.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 May; Vol. 28 (10), pp. e18381.
DOI: 10.1111/jcmm.18381
Abstrakt: Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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