Characterization of fibroblast-specific protein 1 in pulmonary fibrosis
Characterization of fibroblast-specific protein 1 in pulmonary fibrosis
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DOI：
10.1164/rccm.200311-1535oc
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发表时间：
2005-04-15
影响因子：
24.7
通讯作者：
Blackwell, TS
中科院分区：
文献类型：
--
作者：
Lawson, WE;Polosukhin, VV;Blackwell, TS
由于成纤维细胞产生胶原蛋白和其他在组织纤维化过程中沉积的细胞外基质成分，因此定义这些细胞的行为对于了解纤维化疾病的发病机制至关重要。我们研究了成纤维细胞特异性蛋白 1 (IFSP1)（钙调蛋白 S100 肌钙蛋白 C 超家族的成员）在鉴定气管内给予博来霉素诱导的肺纤维化小鼠模型中的肺成纤维细胞中的用途。 FSP1 的蛋白和 mRNA 表达在未治疗的肺中最小，但在给予博来霉素后 1 周增加，并且在治疗后 2 周和 3 周仍保持增加。免疫组织化学显示，博来霉素治疗后，肺部FSP1(+)细胞数量呈剂量依赖性增加。 α1 前胶原和 FSP1 在间质细胞中的共定位表明，FSP1(+) 成纤维细胞在给予博来霉素后有助于胶原蛋白的沉积。在原代肺细胞培养物中，肺成纤维细胞表达 FSP1，但巨噬细胞或 II 型肺泡上皮细胞不表达。 FSP1 还在患有普通间质性肺炎的患者肺活检标本中鉴定出了成纤维细胞。因此，FSP1 是一种改进的肺成纤维细胞标记物，可用于研究肺纤维化的发病机制。
Because fibroblasts produce Collagen and other extracellular matrix components that are deposited during tissue fibrosis, defining the behavior of these cells is critical to understanding the pathogenesis of fibrotic diseases. We investigated the utility of fibroblast-specific protein 1 (IFSP1), a member of the calmodulin S100 troponin C superfamily, for identifying lung fibroblasts in a murine model of pulmonary fibrosis induced by intratracheal administration of bleomycin. Protein and mRNA expression of FSP1 was minimal in untreated lungs, but increased by 1 week after bleomycin administration and remained increased at 2 and 3 weeks after treatment. By immunohistochemistry, the number of FSP1(+) cells increased in a dose-dependent manner in the lungs after bleomycin treatment. Colocalization of alpha 1 procollagen and FSP1 in interstitial cells demonstrated that FSP1(+) fibroblasts contribute to the deposition of Collagen after bleomycin administration. In primary lung cell cultures, lung fibroblasts, but not macrophages or type II alveolar epithelial cells, expressed FSP1. FSP1 also identified fibroblasts in lung biopsy specimens from patients with documented usual interstitial pneumonitis. Therefore, FSP1 is an improved marker for lung fibroblasts that could be useful for investigating the pathogenesis of pulmonary fibrosis.