Transforming growth factor-β and renal fibrosis.
- Author:
Xiao-Ming MENG
1
,
2
,
3
;
Hui-Yao LAN
4
,
5
Author Information
1. School of Pharmacy, Anhui Medical University
2. Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education
3. The Key Laboratory of Major Autoimmune Diseases, Hefei 230032, China.
4. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
5. Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518172, China. hylan@cuhk.edu.hk.
- Publication Type:Journal Article
- MeSH:
Epigenesis, Genetic;
Fibrosis;
Humans;
Kidney Diseases;
pathology;
Signal Transduction;
Smad3 Protein;
metabolism;
Smad7 Protein;
metabolism;
Transforming Growth Factor beta;
metabolism
- From:
Acta Physiologica Sinica
2018;70(6):612-622
- CountryChina
- Language:Chinese
-
Abstract:
Transforming growth factor-β (TGF-β) is a driving force of renal fibrosis, which may lead to chronic kidney diseases and even end stage renal diseases. By activating canonical and non-canonical signaling pathways, TGF-β promotes the synthesis of extracellular matrix while preventing their degradation. In the injured kidney, TGF-β induces apoptosis, proliferation and fibrotic response of renal cells including epithelial cells, endothelial cells, podocytes, fibroblasts, pericytes and macrophages, and it also promotes transdifferentiation, activation and proliferation of myofibroblasts. Additionally, TGF-β exerts profibrotic effects by interplaying with other signaling pathways like BMP-7, Wnt/β-catenin and MAP kinase. Smad3 is the central pathological gene in renal fibrosis, and epigenetic regulation of TGF-β/Smad3 is a hot topic in kidney field. Although direct targeting TGF-β may cause side effects including tumorigenesis and immune diseases, the therapeutic strategies targeting the balance of downstream Smad3 and Smad7 may prevent or delay the progression of fibrotic kidney disease.
