当前位置: 首页 > 文章 > 二甲双胍抑制皮肤成纤维细胞活化的作用机制研究 扬州大学学报(农业与生命科学版) 2019 (4) 49-54
Position: Home > Articles > The study on the effect and mechanism of metformin in attenuating the activation of skin fibroblasts Journal of Yangzhou University(Agricultural and Life Science Edition) 2019 (4) 49-54

二甲双胍抑制皮肤成纤维细胞活化的作用机制研究

作  者:
杜志民;吴梦旖;赵晗;石祥广;吴文育;王久存;刘庆梅
单  位:
上海市延安中学;复旦大学生命科学学院;复旦大学附属华山医院
关键词:
成纤维细胞;二甲双胍;皮肤纤维化;胶原蛋白;TGF-β
摘  要:
为探讨二甲双胍抑制皮肤成纤维细胞活化的作用及机制,利用细胞实时分析检测系统检测二甲双胍对体外培养的皮肤成纤维细胞HFF-1增殖的影响,确定体外最适药物浓度;通过Real-time PCR检测二甲双胍对原代培养的硬皮病患者皮肤成纤维细胞中胶原及纤维化相关基因表达的影响,进一步检测二甲双胍对TGF-β诱导后的正常皮肤成纤维细胞HFF-1中纤维化相关基因表达的作用;通过Western blot检测二甲双胍对I型胶原蛋白表达的作用;通过Sircolassay检测二甲双胍对细胞上清中分泌的胶原蛋白的影响。结果表明:二甲双胍可抑制皮肤成纤维细胞增殖,且具有剂量依赖性;与对照组相比,二甲双胍可降低成纤维细胞中纤维化相关基因表达及细胞上清中胶原蛋白含量。此外,二甲双胍可显著下调TGF-β诱导的纤维化相关基因及胶原蛋白的表达。这一研究提示二甲双胍可能通过抑制成纤维细胞活化而抑制纤维化。
译  名:
The study on the effect and mechanism of metformin in attenuating the activation of skin fibroblasts
作  者:
DU Zhimin;WU Mengyi;ZHAO Han;SHI Xiangguang;WU Wenyu;WANG Jiucun;LIU Qingmei;School of Life Science, Fudan University;Shanghai Yan'an School;Huashan Hospital Affiliated to Fudan University;
关键词:
HFF fibroblasts;;metformin;;skin fibrosis;;collagen;;TGF-β
摘  要:
The method of the real-time cell assay was applied to investigate the influence of metformin on the proliferation of fibroblasts(HFF-1) and to determine the optional drug concentration of metformin in vitro and Real-time PCR was performed to evaluate the effects of metformin on the expression of collagen genes and fibrosis-related genes in Primary cultured scleroderma skin fibroblast, and the same approach was utilized to further detection of the effects of metformin on the expression of the above fibrosis-related genes induced by TGF-β in HFF-1 cells. Western Blot was used to explore the effects of metformin on the expression of type I collagen. Sircol assay was employed to investigate the influence of metformin on collagen secretion. The objective of the study was to investigate the effect and mechanism of metformin in attenuating the activation of skin fibroblast. The results demonstrated that metformin could inhibit the proliferation of skin fibroblasts in a dose-dependent manner. Compared with the control group, metformin had the ability of reducing the expression of fibrosis-related genes in fibroblasts and the content of collagen in cell supernatant. In addition, metformin significantly down-regulated the expression of fibrosis-related genes and collagen in HFF-1 cells induced by TGF-β. The results revealed that the suppression of metformin on fibrosis is related to the way of restraining the activation of fibroblasts.

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