Different effects of growth factors on proliferation and matrix production of normal and fibrotic human lung fibroblasts
Different effects of growth factors on proliferation and matrix production of normal and fibrotic human lung fibroblasts
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DOI：
10.1007/s00408-004-2534-z
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发表时间：
2005-07-01
期刊：
影响因子：
5
通讯作者：
Faehling, M
中科院分区：
文献类型：
--
作者：
Hetzel, M;Bachem, M;Faehling, M
目标和方法：在特发性肺纤维化（IPF）中，成纤维细胞增殖和基质沉积增加导致肺损伤和呼吸功能不全。我们从健康成人和三名IPF患者的肺活检组织中培养人成纤维细胞，（组织学上常见的肺部肺炎，UIP），以比较增殖（[H-3]胸苷掺入，细胞计数）和基质蛋白表达（免疫荧光，使用时间分辨免疫荧光定量纤连蛋白合成）的正常和UIP成纤维细胞响应于各种生长因子。生长因子血小板衍生生长因子-BB（PDGF）、表皮生长因子（EGF）、胰岛素生长因子-1（IGF-1）、胰岛素样生长因子-2（IGF-2）、肿瘤坏死因子α（TNF-α）、（TNF α），转化生长因子-β TGF β（1）和成纤维细胞生长因子-2（FGF-2）刺激正常肺成纤维细胞的增殖显著高于UIP成纤维细胞的增殖。免疫荧光显示血清、TGF β 1和TNF α诱导的I型胶原、III型胶原和纤连蛋白的广泛表达。这种表达在UIP成纤维细胞中比在正常成纤维细胞中更明显。纤连蛋白合成的定量显示UIP成纤维细胞响应于PDGF、EGF、IGF-1、IGF-2、TNF α、TGF β（1）和FGF-2而增强的纤连蛋白合成。结论：来自正常和UIP肺的成纤维细胞在它们对生长因子的响应方面不同：正常成纤维细胞显示主要的增殖反应，而UIP成纤维细胞显示增强的合成活性。不同的成纤维细胞反应可能导致UIP患者进行性肺纤维化。
Objectives and methods: In idiopathic pulmonary fibrosis (IPF), proliferation of fibroblasts and increased matrix deposition result in pulmonary damage and respiratory insufficiency. We cultured human fibroblasts from lung biopsies of healthy adults and of three patients with IPF (histologically usual interstital pneumonitis, UIP) in order to compare proliferation ([H-3]thymidine incorporation, cell count) and matrix protein expression (immune fluorescence, quantification of fibronectin synthesis using time-resolved immune fluorescence) of normal and UIP fibroblasts in response to various growth factors.Findings: The growth factors platelet-derived growth factor-BB (PDGF), epidermal growth factor (EGF), insulin growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), tumor necrosis factor alpha (TNF alpha), Transforming growth factor-beta (TGF beta(1)), and fibroblast growth factor-2 (FGF-2) stimulate proliferation of normal lung fibroblasts significantly more than proliferation of UIP fibroblasts. Immunofluorescence reveals extensive expression of collagen I, collagen III, and fibronectin induced by serum, TGF beta(1), and TNF alpha. This expression is more pronounced in UIP fibroblasts than in normal fibroblasts. Quantification of fibronectin synthesis reveals an enhanced fibronectin synthesis by UIP fibroblasts in response to PDGF, EGF, IGF-1, IGF-2, TNF alpha, TGF beta(1), and FGF-2).Conclusions: Fibroblasts from normal and UIP lungs differ in their response to growth factors: Whereas normal fibroblasts show a predominantly proliferative response, UIP fibroblasts show an enhanced synthetic activity. Different fibroblast responses may contribute to progressive pulmonary fibrosis in patients with UIP.