DIFFERENTIAL COLLAGEN AND FIBRONECTIN PRODUCTION BY THY1+ AND THY1- LUNG FIBROBLAST SUBPOPULATIONS
DIFFERENTIAL COLLAGEN AND FIBRONECTIN PRODUCTION BY THY1+ AND THY1- LUNG FIBROBLAST SUBPOPULATIONS
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DOI：
10.1152/ajplung.1992.263.2.l283
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发表时间：
1992-08-01
影响因子：
--
通讯作者：
PHIPPS, RP
中科院分区：
文献类型：
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作者：
DERDAK, S;PENNEY, DP;PHIPPS, RP
肺纤维化是由多种病因引起的，其特征是成纤维细胞增殖和间质胶原过度积聚。纤维化是否与胶原合成量或类型不同的成纤维细胞亚群的选择性扩增有关尚不清楚。我们以前已经分离出的线和克隆的正常小鼠肺成纤维细胞的存在下的Thy 1表面抗原的基础上。这些亚群在形态、生长特征和II类主要组织相容性复合物抗原的显示上不同（R。Phipps，D. P. Penney，P. Keng，H. Quill，A. Paxia，S. Derdak和M. E.费尔奇Am. J.呼吸。细胞分子1：65-74，1989）。我们评估了Thy 1+（Fib 2-T-3+）和Thy 1-（Fib 2-T-4-）肺成纤维细胞系和克隆合成的胶原和纤连蛋白的量和类型。Thy 1+成纤维细胞系合成的胶原和非胶原蛋白比Thy 1-系多2 - 3倍。相比之下，Thy 1+和Thy 1-细胞系合成了相似量的纤连蛋白。Thy 1+和Thy 1-细胞系和克隆表达α-1（I）-和α-1（III）-前胶原的mRNA，并合成两种类型（主要是I型和少量III型）的胶原、蛋白质和mRNA。成纤维细胞克隆在总胶原蛋白和纤连蛋白的产生方面变化显著，其中一个Thy 1-克隆（D3）合成最大量的胶原蛋白，但相对较少的纤连蛋白。这些观察结果表明Thy 1+和Thy 1-肺成纤维细胞亚群的胶原蛋白和纤连蛋白产生具有显著的异质性，并支持这样的假设，即功能不同的成纤维细胞亚群在体内的选择性扩增，可能在炎性细胞因子的影响下，可能在肺纤维化的发病机制中发挥不可或缺的作用。
Pulmonary fibrosis resulting from diverse etiologies is characterized by proliferation of fibroblasts and excessive accumulation of interstitial collagen. Whether fibrosis is associated with selective expansion of fibroblast subpopulations differing in amounts or types of collagens synthesized is unknown. We have previously isolated lines and clones of normal murine lung fibroblasts based on the presence of the Thy 1 surface antigen. These subpopulations differ in morphology, growth characteristics, and display of class II major histocompatibility complex antigens (R. P. Phipps, D. P. Penney, P. Keng, H. Quill, A. Paxhia, S. Derdak, and M. E. Felch. Am. J. Respir. Cell Mol. Biol. 1: 65-74, 1989). We evaluated the amounts and types of collagen and fibronectin synthesized by Thy 1+ (Fib2-T-3+) and Thy 1- (Fib2-T-4-) lung fibroblast lines and clones. Thy 1+ fibroblast line synthesized two- to threefold more collagen and noncollagen protein than the Thy 1- line. In contrast, both the Thy 1+ and Thy 1- lines synthesized similar amounts of fibronectin. Thy 1+ and Thy 1- lines and clones expressed mRNA for alpha-1(I)-and alpha-1(III)-procollagen and synthesized both types (predominately type I and lesser amounts of type III) of collagen, protein, and mRNA. The fibroblast clones varied significantly in total collagen and fibronectin production, with one Thy 1- clone (D3) synthesizing the largest amount of collagen but relatively little fibronectin. These observations indicate a significant heterogeneity in collagen and fibronectin production by Thy 1+ and Thy 1- lung fibroblast subpopulations and support the hypothesis that selective expansion of functionally distinct fibroblast subsets in vivo, perhaps under the influence of inflammatory cytokines, may play an integral role in the pathogenesis of pulmonary fibrosis.