文章摘要

纤维细胞生长因子1对转化生长因子β1诱导的人肾成纤维细胞活化纤维化的保护作用

作者: 1王玉路, 1薛现军, 1刘敏洁, 1苗月亭
1 濮阳市油田总医院肾内科,河南 濮阳 457001
通讯: 王玉路 Email: wangyuluccxx@163.com
DOI: 10.3978/j.issn.2095-6959.2019.12.002

摘要

目的:探讨纤维细胞生长因子1(fibroblast growth factor 1,FGF1)对转化生长因子β1(transforming growth factor β1,TGF-β1)诱导的人肾成纤维细胞活化纤维化的保护作用及机制。方法:将NRK-49F细胞过表达FGF1后,用2 ng/mL TGF-β1刺激诱导肾纤维化模型。24 h后观察细胞密度及BrdU阳性率;MTT法测定细胞活力;细胞免疫荧光和蛋白质印迹法检测NRK-49F细胞中α-SMA和FN蛋白表达水平;细胞免疫荧光和蛋白质印迹法检测NRK-49F细胞中p-S6,p-Akt(Ser473),β-catenin和p-Smad3(Ser423/425)蛋白的表达和分布的变化。结果:外源性TGF-β1促进肾成纤维细胞体外增殖,而过表达FGF1可以降低TGF-β1诱导的肾成纤维细胞增殖,减轻由TGF-β1处理刺激的肾成纤维细胞活化;FGF1过表达可以抑制TGF-β1诱导的Akt/β-catenin改变,但不抑制Smad信号转导。结论:FGF1可能是通过Akt/β-catenin通路实现对TGF-β1诱导的人肾成纤维细胞活化纤维化的保护作用。
关键词: 纤维细胞生长因子1;肾纤维化;Akt;β-catenin

Protective effect of fibroblast growth factor 1 on transforming growth factor β1 induced activation of human renal fibroblasts

Authors: 1WANG Yulu, 1XUE Xianjun, 1LIU Minjie, 1MIAO Yueting
1 Department of Nephrology, Puyang Oilfield General Hospital, Puyang Henan 457001, China

CorrespondingAuthor: WANG Yulu Email: wangyuluccxx@163.com

DOI: 10.3978/j.issn.2095-6959.2019.12.002

Abstract

Objective: To investigate the protective effect and mechanism of fibroblast growth factor 1 (FGF1) on transforming growth factor β1 (TGF-β1)-induced activation of human renal fibroblasts. Methods: NRK-49F cells were over-expressed with FGF1 and then stimulated with 2 ng/mL TGF-β1 to induce renal fibrosis model. Cell density and BrdU positive rate were observed after 24 h. The cell viability was determined by MTT assay. The expressions of α-SMA and FN protein in NRK-49F cells were detected by immunofluorescence and Western blot. The changes of p-S6, p-Akt (Ser473), β-catenin and p-Smad3 (Ser423/425) in NRK-49F cells were detected by immunofluorescence and Western blot. Results: Exogenous TGF-β1 promoted the proliferation of renal fibroblasts in vitro, while over-expression of FGF1 reduced TGF-β1-induced renal fibroblast proliferation and reduced renal fibroblast activation stimulated by TGF-β1. Over-expression of FGF1 inhibited TGF-β1-induced Akt/β-catenin alteration, but did not inhibit Smad signaling. Conclusion: The protective effect of FGF1 on TGF-β1-induced activation of human renal fibroblasts may be achieved through the Akt/ β-catenin pathway.
Keywords: fibroblast growth factor 1; renal fibrosis; Akt; β-catenin