Pulmonary and activation-regulated chemokine stimulates collagen production in lung fibroblasts
Pulmonary and activation-regulated chemokine stimulates collagen production in lung fibroblasts
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DOI：
10.1165/rcmb.2003-0078oc
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发表时间：
2003-12-01
影响因子：
6.4
通讯作者：
White, B
中科院分区：
文献类型：
--
作者：
Atamas, SP;Luzina, IG;White, B
肺纤维化患者肺中肺和活化调节趋化因子（PARC） mRNA和蛋白水平升高。本研究的目的是确定PARC是否可以通过刺激肺成纤维细胞中胶原蛋白的产生直接参与肺纤维化的发展。暴露于PARC可使正常成人肺和真皮成纤维细胞中胶原mRNA和蛋白的产生增加3- 4倍。PARC激活3 ~ 6 h后，胶原mRNA瞬间升高，激活24 h后胶原蛋白含量升高。同时，PARC对成纤维细胞增殖的影响不太明显，与对照非刺激细胞相比，增幅不超过50%。在成纤维细胞中，PARC细胞内信号传导导致ERK1/2激活，但不激活p38；ERK的药理学抑制，而不是p38，也阻断了PARC对胶原生成的影响。百日咳毒素抑制实验表明PARC受体是G蛋白偶联的。因此，PARC是直接作为促纤维化因子的CC趋化因子家族的成员。
Levels of pulmonary and activation-regulated chemokine (PARC) mRNA and protein are increased in the lungs of patients with pulmonary fibrosis. The purpose of this study was to establish whether PARC could be directly involved in development of pulmonary fibrosis by stimulating collagen production in lung fibroblasts. Exposure to PARC increased production of collagen mRNA and protein by 3- to 4-fold in normal adult lung and dermal fibroblast cells. Collagen mRNA transiently increased after 3-6 h of activation with PARC, with an increase in collagen protein detected after 24 h of activation. At the same time, PARC had less pronounced effect on fibroblast proliferation, not exceeding 50% increase over control nonstimulated cells. PARC intracellular signaling led to activation of ERK1/2, but not p38, in fibroblasts; pharmacologic inhibition of ERK, but not p38, also blocked PARC's effect on collagen production. Inhibition experiments with pertussis toxin suggested that PARC receptor is G protein-coupled. Thus, PARC is a member of the CC chemokine family that acts directly as a profibrotic factor.