Immunohistochemical study of cell cycle regulators in idiopathic pulmonary fibrosis

特发性肺纤维化（IPF）是一种以成纤维细胞增殖为特征的进行性纤维化疾病。IPF中的成纤维细胞增殖通常被认为是上皮损伤和肺泡炎后的一个过程，但其机制的细节仍有待阐明。细胞周期蛋白依赖性激酶（Cyclin dependent kinase， CDK）和肿瘤抑制基因CDK抑制剂调控细胞周期并参与细胞增殖。在此基础上，我们推测IPF成纤维细胞存在细胞周期调节因子的异常。在本报告中，我们利用免疫组织化学方法检测了IPF患者手术切除肺组织中pRB（视网膜母细胞瘤基因产物）和p27的表达水平，这两种基因在一个主要的肿瘤抑制通路（RB通路）中起着核心作用。与邻近组织相比，pRB在成纤维细胞灶中的表达降低，而p27的表达没有变化。这些结果表明，成纤维细胞灶中pRB的下调参与了IPF的发病机制。

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disorder characterized by the proliferation of fibroblasts. Fibroblast proliferation in IPF is generally observed as a process following epithelial injury and alveolitis, but details of the mechanism remain to be clarified.Cyclin dependent kinase (CDK) and the tumor suppressor gene, CDK inhibitor regulate cell cycle and are implicated in cell proliferation. On this basis, we hypothesized that fibroblasts in IPF have an abnormality of cell cycle regulating factors. In this report, we utilized immunohistochemistry to examine the level of expression of pRB(retinoblastoma gene product) and p27, both of which play central roles in a major tumor suppressive pathway (RB pathway), in surgically resected lung tissues of patients with IPF. The expression of pRB was reduced in fibroblastic foci compared with the adjacent tissues, while the expression of p27 did not vary. That results suggest that downregulation of pRB in fibroblastic foci contribute to the pathogenesis of IPF.