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Macrophage migration-inhibitory factor induces myofibroblastic phenotype transformation of human embryonic lung fibroblasts via Rho-kinase in vitro
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- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF PATHOPHYSIOLOGY
- Issue:
- 11
- DOI:
- 10.3969/j.issn.1000-4718.2012.11.004
- Key Word:
- 巨噬细胞移动抑制因子;成纤维细胞;肌成纤维细胞;α-平滑肌肌动蛋白;Rho相关激酶类
Abstract： 目的:观察重组巨噬细胞移动抑制因子(rMIF)对人胚肺成纤维细胞(MRC-5)表型转换的作用,探讨哮喘气道重塑的发生机制.方法:不同浓度的rMIF (25～100 μg/L)分别作用于MRC-5细胞24 h或48 h,RT-PCR法检测α-平滑肌肌动蛋白(α-SMA) mRNA表达,Western blotting检测α-SMA蛋白合成;100 μg/L rMIF刺激MRC-5细胞48 h,刺激前0.5 h加入Rho拮抗剂Y27632,RT-PCR法检测α-SMA mRNA表达,Western blotting法检测α-SMA表达;100 μg/L rMIF分别刺激MRC-5 6 h、12 h、24 h或48 h,Western blotting检测磷酸化肌球蛋白磷酸酶目标亚单位1(p-MYP1)蛋白合成.结果:刺激MRC-5 24 h,不同浓度的rMIF对α-SMA mRNA转录未见显著影响(P>0.05).刺激MRC-5细胞48 h,rMIF可呈剂量依赖地促进α-SMA mRNA(r=0.697,P<0.01)和蛋白(r=0.957,P<0.01)表达.Y27632预刺激后,显著抑制rMIF100 μg/L促进α-SMA mRNA和蛋白表达的作用(均P<0.01).rMIF刺激6 h后,p-MYPT1表达显著增加(P< 0.01),12 h达到高峰(P<0.01),24 h开始下降,但24 h和48 h其水平仍高于对照组(均P<0.01).结论:rMIF通过Rho信号通路刺激成纤维细胞表型转化,可能在哮喘气道重塑的发病机制中发挥关键作用.
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