Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, PR China.
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of Agricultural Biological Functional Gene, Harbin, 150030, PR China.
Biomed Pharmacother. 2017 Sep;93:695-704. doi: 10.1016/j.biopha.2017.06.100. Epub 2017 Jul 8.
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.
成纤维细胞生长因子 21（FGF21）是成纤维细胞生长因子家族的一员，作为葡萄糖和脂质稳态的有效调节剂发挥作用，但它对肾纤维化的影响及其潜在机制尚不清楚。本研究旨在探讨 FGF21 是否对高糖诱导的人肾小球系膜细胞（HMC）纤维化有影响及其潜在机制。众所周知，高糖可刺激人肾小球系膜细胞细胞外基质（ECM）的表达。在人类中，ECM 的过度表达和沉积导致肾纤维化。因此，在这项研究中，将 HMC 孵育在高糖中，并加入或不加入不同浓度的 FGF21。结果表明，FN、Col、TGFβ1 和α-SMA 的表达在 HMC 中显著上调。然而，FGF21 的治疗下调了 FN、Col、TGFβ1 和α-SMA 的表达。此外，生长因子被认为是肾纤维化发病机制的重要驱动力。在高糖诱导的 HMC 中发现 PDGF、VEGF 和 CTGF 的表达显著增加。FGF21 治疗通过下调 STAT5 的磷酸化水平显著降低了这些生长因子的表达。在这里，我们首次报道 FGF21 通过抑制 STAT5 信号通路降低 ECM 表达，从而降低 PDGF、VEGF 和 CTGF 的表达。
