Advances in transforming growth factor-β1 mediated non-canonical signaling pathways in renal fibrosis
10.12025/j.issn.1008-6358.2026.20251014
- VernacularTitle:转化生长因子β1介导的非经典信号通路在肾纤维化中的研究进展
- Author:
Xiaonan LIU
1
;
Jun ZOU
2
Author Information
1. Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China.
2. Department of Nephrology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
- Publication Type:Review
- Keywords:
kidney;
fibrosis;
chronic kidney disease;
transforming growth factor-β1;
molecular mechanism
- From:
Chinese Journal of Clinical Medicine
2026;33(3):516-525
- CountryChina
- Language:Chinese
-
Abstract:
Renal fibrosis represents the pivotal pathological process driving the progression of chronic kidney disease (CKD) towards end-stage renal disease. Its core manifestations include chronic inflammation, excessive deposition of extracellular matrix (ECM), and tubulointerstitial injury resulting in functional deterioration. Emerging research on the molecular mechanisms underlying renal fibrosis has established that, beyond the canonical Smad-dependent pathway, transforming growth factor-β1 (TGF-β1) also modulates fibrogenesis through non-canonical signaling pathways, notably the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascades. These non-canonical pathways engage in crosstalk with the canonical Smad pathway, synergistically regulating key processes such as ECM metabolism, inflammatory responses, and epithelial-mesenchymal transition (EMT), thereby collectively orchestrating the initiation and progression of renal fibrosis. Notably, various active components derived from traditional Chinese medicine have demonstrated anti-fibrotic efficacy by modulating these pathways, highlighting their promising multi-target therapeutic potential. This review aims to systematically summarize recent advances in understanding the roles of TGF-β1-mediated MAPK and PI3K/Akt non-canonical signaling pathways in renal fibrosis and to discuss potential therapeutic strategies targeting these pathways.
