Fibroblast growth factor 21 ameliorates high glucose-induced fibrogenesis in mesangial cells through inhibiting STAT5 signaling pathway.

Abstract

Fibroblast growth factor 21 (FGF21) is a member of the FGF family and acts as a potent regulator of glucose and lipid homeostasis, but its effect on renal fibrosis and the underlying mechanisms are totally unknown. The purpose of this study was designed to investigate whether FGF21 has effect on high glucose-induced fibrogenesis in human mesangial cells (HMCs) and the underlying mechanism. High glucose is well known to stimulate the expression of extracelluar matrix (ECM) in human mesangial cells. In humans, overexpression and deposition of ECM lead to renal fibrosis. Thus, in this study, HMCs were incubated in high glucose with or without various concentrations of FGF21. Results demonstrated that the expression of FN, Col, TGF β1 and α-SMA were significantly up-regulated in HMCs. Whereas, treatment with FGF21 down-regulated the expression of FN, Col, TGF β1 and α-SMA. In addition, growth factors are considered to be an important driving force for the pathogenesis of renal fibrosis. Significantly increased PDGF, VEGF and CTGF expression were found in HMCs induced by high glucose. FGF21 treatments significantly decreased these growth factors expression by down-regulating the phosphorylation level of STAT5. Here, we reported for the first time that FGF21 decreases ECM expression by inhibiting STAT5 signal pathway and consequently decreasing the expression of PDGF, VEGF and CTGF.

• Authors: Shuai Li, Xiaochen Guo, Teng Zhang, Nan Wang, Junyan Li, Pengfei Xu, Shengqi Zhang, Guiping Ren, Deshan Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 93 Pg. 695-704 (Sep 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28692941 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• STAT5 Transcription Factor
• Transforming Growth Factor beta1
• Vascular Endothelial Growth Factor A
• fibroblast growth factor 21
• Connective Tissue Growth Factor
• Fibroblast Growth Factors
• Glucose

Topics

• Cells, Cultured
• Connective Tissue Growth Factor (metabolism)
• Down-Regulation (physiology)
• Extracellular Matrix (metabolism)
• Fibroblast Growth Factors (metabolism)
• Fibrosis (metabolism)
• Glucose (metabolism)
• Humans
• Mesangial Cells (metabolism)
• Phosphorylation (physiology)
• STAT5 Transcription Factor (metabolism)
• Signal Transduction (physiology)
• Transforming Growth Factor beta1 (metabolism)
• Up-Regulation (physiology)
• Vascular Endothelial Growth Factor A (metabolism)