Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis
Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis
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DOI：
10.1152/ajplung.1998.275.2.l365
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发表时间：
1998-08-01
影响因子：
4.9
通讯作者：
Friedman, M
中科院分区：
文献类型：
--
作者：
Lasky, JA;Ortiz, LA;Friedman, M
结缔组织生长因子（CTGF）是一种新描述的38-kDa肽类成纤维细胞有丝分裂原，也是皮肤结缔组织沉积的促进剂。CTGF基因启动子含有转化生长因子-β 1（TGF-β 1）反应元件。由于TGF-β 1表达在几种纤维增生性肺病模型中上调，我们询问CTGF是否在鼠肺纤维化模型中也上调，以及CTGF是否可以介导与TGF-β 1相关的一些纤维化作用。克隆大鼠CTGF基因的一部分，并用于显示鼠和人肺成纤维细胞的原代分离物在体外表达CTGF mRNA。在体外加入TGF-β 1后2、4和24 h，人和鼠肺成纤维细胞中CTGF表达增加了两倍以上。博莱霉素敏感小鼠品系（C57 BL/6）和博莱霉素抗性小鼠品系（BALB/c）给予博莱霉素，一种已知的肺纤维化剂。CTGF mRNA表达上调的敏感，但不是在耐药，博莱霉素给药后的小鼠品系。两种小鼠品系之间CTGF表达的体内差异不是由于BALB/c肺成纤维细胞对TGF-β 1应答的固有能力，因为来自未处理的BALB/c小鼠肺的成纤维细胞在体外用TGF-β 1处理时上调了它们的CTGF信息。这些数据表明，CTGF在肺成纤维细胞中表达，并可能在肺纤维化的发病机制中发挥作用。
Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-beta 1 (TGF-beta 1) response element. Because TGF-beta 1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-beta 1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF-beta 1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin-resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGF-beta 1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-beta 1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.