REGULATION OF FIBROBLAST PROCOLLAGEN PRODUCTION - TRANSFORMING GROWTH FACTOR-BETA(1) INDUCES PROSTAGLANDIN E(2) BUT NOT PROCOLLAGEN SYNTHESIS VIA A PERTUSSIS-TOXIN-SENSITIVE G-PROTEIN
REGULATION OF FIBROBLAST PROCOLLAGEN PRODUCTION - TRANSFORMING GROWTH FACTOR-BETA(1) INDUCES PROSTAGLANDIN E(2) BUT NOT PROCOLLAGEN SYNTHESIS VIA A PERTUSSIS-TOXIN-SENSITIVE G-PROTEIN
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DOI：
10.1042/bj3070063
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发表时间：
1995-04-01
影响因子：
4.1
通讯作者：
LAURENT, GJ
中科院分区：
文献类型：
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作者：
MCANULTY, RJ;CHAMBERS, RC;LAURENT, GJ
转化生长因子-β(1) (TGF beta(1)) 启动一系列信号事件，导致不同的细胞反应，包括刺激细胞外基质蛋白的产生。在这项研究中，我们研究了百日咳毒素敏感 G 蛋白在介导 TGF beta(1) 对成纤维细胞前胶原代谢的影响中的作用。 TGF beta(1) 以剂量依赖性方式刺激人胎肺成纤维细胞前胶原的合成和产生，最大浓度为 0.5 ng/ml。 TGF beta(1) 还降低了细胞内降解的新合成前胶原的比例。百日咳毒素（一种 G 蛋白抑制剂）进一步刺激 TGF beta(1) 诱导的前胶原合成和产生，但单独使用对成纤维细胞前胶原代谢没有影响。添加吲哚美辛还增强了 TGF beta(1) 诱导的前胶原合成和产生的增加。百日咳毒素和吲哚美辛的作用不相加。百日咳毒素和吲哚美辛不影响对照细胞在细胞内降解的新合成的前胶原的比例，无论是单独的还是组合的。 TGFβ(1)诱导的细胞内前胶原降解的减少得以维持，但不受百日咳毒素或吲哚美辛的进一步影响。与对照细胞的 PGE(2) 产生相比，TGF beta(1) 增加了前列腺素 E(2) (PGE(2)) 的产生。添加百日咳毒素或吲哚美辛可阻断 TGF beta(1) 诱导的 PGE(2) 产生增加。 TGF beta(1) 诱导的 PGE(2) 增加先于前胶原生成的增加。这些结果表明，TGF beta(1) 诱导的肺成纤维细胞的前胶原合成受到 PGE(2) 产生的调节。百日咳毒素和吲哚美辛可阻断 PGE(2) 的产生并增强 TGF beta(1) 对前胶原合成的作用。根据这些数据，我们得出结论，TGF beta(1) 对 PGE(2) 产生而非前胶原合成的影响是通过与百日咳毒素敏感 G 蛋白相连的受体介导的。
Transforming growth factor-beta(1) (TGF beta(1)) initiates a series of signalling events resulting in diverse cellular responses including stimulation of extracellular matrix protein production. In this study we have investigated the role of pertussis toxin-sensitive G-proteins in mediating the effects of TGF beta(1) on fibroblast procollagen metabolism. TGF beta(1) stimulated human fetal lung fibroblast procollagen synthesis and production in a dose-dependent manner which was maximal at 0.5 ng/ml. TGF beta(1) also decreased the proportion of newly synthesized procollagen degraded intracellularly. Pertussis toxin, a G-protein inhibitor, further stimulated TGF beta(1)-induced procollagen synthesis and production, but alone it had no effect on fibroblast procollagen metabolism. Addition of indomethacin also potentiated the TGF beta(1)-induced increase in procollagen synthesis and production. The effects of pertussis toxin and indomethacin were not additive. Pertussis toxin and indomethacin did not affect the proportion of newly synthesized procollagen degraded intracellularly, either alone or in combination, by control cells. The TGF beta(1)-induced decrease in intracellular procollagen degradation was maintained but not further affected by pertussis toxin or indomethacin. TGF beta(1) increased prostaglandin E(2) (PGE(2)) compared with PGE(2) production by control cells. Addition of pertussis toxin or indomethacin blocked the TGF beta(1)-induced increase in PGE(2) production. The TGF beta(1)-induced increase in PGE(2) preceded the increase in procollagen production. These results demonstrate that TGF beta(1)-induced procollagen synthesis by lung fibroblasts is modulated by production of PGE(2). Pertussis toxin and indomethacin block the production of PGE(2) and enhance the effect of TGF beta(1) on procollagen synthesis. From these data we conclude that the effects of TGF beta(1) on PGE(2) production but not procollagen synthesis are mediated via a receptor linked to a pertussis toxin-sensitive G-protein.