Hydrogen sulfide suppresses migration, proliferation and myofibroblast transdifferentiation of human lung fibroblasts
Hydrogen sulfide suppresses migration, proliferation and myofibroblast transdifferentiation of human lung fibroblasts
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DOI：
10.1016/j.pupt.2009.07.003
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发表时间：
2009-12-01
影响因子：
3.2
通讯作者：
Liu, Xin-Min
中科院分区：
文献类型：
--
作者：
Fang, Li-Ping;Lin, Qing;Liu, Xin-Min
我们曾报道硫化氢(H_2S)参与了博莱霉素诱导的大鼠肺纤维化的发病机制，但其作用的细胞机制尚不清楚。本研究旨在探讨外源性H_2S在胎牛血清(FBS)和生长因子诱导的人肺成纤维细胞(MRC5)迁移、增殖和转分化中的作用，以阐明H_2S抑制肺纤维化发生的机制。结果发现，硫化氢可显著降低胎牛血清和碱性成纤维细胞生长因子刺激的MRC5细胞迁移距离，抑制胎牛血清和血小板衍生生长因子BB诱导的MRC5细胞增殖，并抑制转化生长因子-β1诱导的MRC5细胞向肌成纤维细胞的转分化。此外，硫化氢预育可降低胎牛血清、PDGF-BB、转化生长因子-β1和碱性成纤维细胞生长因子诱导的MRC5细胞胞外信号调节激酶(ERK1/2)的磷酸化。然而，ATP敏感性钾通道(K-ATP)阻断剂格列本脲不能减弱硫化氢对MRC5细胞迁移、增殖和肌成纤维细胞转分化的抑制作用。因此，硫化氢在体外直接抑制胎牛血清和生长因子刺激的成纤维细胞迁移、增殖和表型转化，这可能是硫化氢抑制肺纤维化的一个重要机制。H_2S对肺成纤维细胞的上述作用至少部分是通过降低ERK的磷酸化来实现的，而不依赖于K-ATP通道的开放。(C)2009爱思唯尔有限公司。保留所有权利。
We previously reported that hydrogen sulfide (H2S) was implicated in the pathogenesis of bleomycin-induced pulmonary fibrosis in rat, but the cellular mechanisms underlying the role it played were not well characterized. The present study was undertaken to investigate the role of the exogenous H2S in human lung fibroblast (MRC5) migration, proliferation and myofibroblast transdifferentiation induced by fetal bovine serum (FBS) and growth factors in vitro, to elucidate the mechanisms by which H2S inhibits pathogenesis of pulmonary fibrosis. We found that H2S incubation significantly decreased the MRC5 cell migration distance stimulated by FBS and basic fibroblast growth factor (bFGF), inhibited MRC5 cell proliferation induced by FBS and platelet-derived growth factor-BB (PDGF-BB), and also inhibited transforming growth factor-beta 1 (TGF-beta 1) induced MRC5 cell transdifferentiation into myofibroblasts. Moreover, preincubation with H2S decreased extracellular signal-regulated kinase (ERK1/2) phosphorylation in MRC5 cells induced by FBS, PDGF-BB, TGF-beta 1, and bFGF. However, the inhibition effects of H2S on MRC5 cell migration, proliferation and myofibroblast transdifferentiation were not attenuated by glibenclamide, an ATP-sensitive K+ channel (K-ATP) blocker. Thus, H2S directly suppressed fibroblast migration, proliferation and phenotype transform stimulated by FBS and growth factors in vitro, which suggests that it could be an important mechanism of H2S-suppressed pulmonary fibrosis. These effects of H2S on pulmonary fibroblasts were, at least in part, mediated by decreased ERK phosphorylation and were not dependent on K-ATP channel opening. (c) 2009 Elsevier Ltd. All rights reserved.