肾上腺髓质素通过Smad2/3信号途径抑制TGF-β1刺激的肺成纤维细胞前胶原蛋白的合成

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英文篇名：Adrenomedullin inhibits TGF-β1-induced procollagen expression in cultured human fetal lung fibroblasts via Smad2/3 pathway 作者：郝淑玲 ; 王卫平 ; 于忠和 ; 李建东 英文作者：HAO Shuling;WANG Weiping;YU Zhonghe;LI Jiandong;Department of Respiratory Disease,Military General Hospital of Beijing PLA;Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Peking University;Department of Oncology Disease,Military General Hospital of Beijing PLA; 关键词：肾上腺髓质素 ; 纤维化 ; 转化生长因子β1 ; 1型前胶原蛋白α1 ; 3型前胶原蛋白α1 ; Smad2/3 英文关键词：adrenomedullin;;fibrosis;;transforming growth factor-β1;;procollagen type 1 α1;;procollagen type 3 α1;;Smad2/3 中文刊名：XBFM 英文刊名：Chinese Journal of Cellular and Molecular Immunology 机构：北京军区总医院呼吸内科;北京大学医学部生化与分子生物学教研室;北京军区总医院肿瘤内科; 出版日期：2014-11-18 出版单位：细胞与分子免疫学杂志 年：2014 期：v.30 基金：国家自然科学基金(30070336) 语种：中文; 页：XBFM201411002 页数：4 CN：11 ISSN：61-1304/R 分类号：9-12

摘要

目的观察肾上腺髓质素(AM)对转化生长因子β1(TGF-β1)促进肺成纤维细胞1型前胶原蛋白α1(Col1α1)、3型前胶原蛋白α1(Col3α1)基因表达及Smad2/3通路的影响,探讨AM对TGF-β1促肺成纤维细胞胶原合成作用的机制。方法体外原代培养人胚肺成纤维细胞(HFLF),利用反转录PCR(RT-PCR)观察AM及TGF-β1对HFLF的Col1α1、Col3α1 mRNA表达的影响;Western blot法观察AM及TGF-β1对HFLF磷酸化Smad2/3(p-Smad2/3)蛋白表达的影响。结果 TGF-β1可以刺激HFLF的Col1α1、Col3α1 mRNA和p-Smad2/3蛋白表达,AM则可抑制基础条件下TGF-β1促进的Col3α1 mRNA表达,同时也抑制Smad2/3蛋白的表达。结论 AM可能通过Smad2/3信号转导途径,抑制TGF-β1促进的HFLF前胶原蛋白的合成作用。
        Objective To observe the effects of adrenomedullin( AM) on transforming growth factor-β1( TGF-β1)induced the expression of procollagen type 1 alpha 1( Col1α1) and procollagen type 3 alpha 1( Col3α1) as well as Smad2 /3phosphorylation in human fetal lung fibroblasts( HFLFs). Methods Primary HFLFs were cultured in vitro. After treated with TGF-β1 and /or AM,the expression levels of Col1α1 and Col3α1 mRNA were determined by reverse transcription PCR( RT-PCR),and phospho-Smad2/3( p-Smad2/3) protein levels in HFLFs were measured by Western blotting. Results TGF-β1 increased the gene expression levels of Col1α1 and Col3α1,and promoted the phosphorylation levels of Smad2 /3protein in HFLFs. AM significantly reversed the expression level of Col3α1 mRNA,and inhibited p-Smad2 /3 expression in HFLFs induced by TGF-β1. Conclusion AM could inhibit TGF-β1-induced the procollagen expression in cultured HFLFs possibly through the Smad2 /3 signaling pathway.

引文

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