Immunohistochemical study of cell cycle regulators in idiopathic pulmonary fibrosis

特发性肺纤维化细胞周期调节因子的免疫组织化学研究

• 批准号: 15590802
• 负责人: CHIDA Kingo
• 金额: $ 1.86万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590802/
• 关键词: idiopathic pulmonary fibrosis; control of cell cycle; fibroblast; 突発性肺線維症; 繊維芽細胞; 細胞周期; RB遺伝子; p53遺伝子

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.

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观察为上皮损伤和肺泡炎后的过程，但其机制的细节仍有待阐明。细胞周期蛋白依赖性激酶（CDK）和肿瘤抑制基因、CDK抑制剂调节细胞周期并参与细胞增殖。在此基础上，我们推测IPF中的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 患者手术切除的肺组织中 pRB（视网膜母细胞瘤基因产物）和 p27 的表达水平，这两者在主要肿瘤抑制途径（RB 途径）中发挥着核心作用。与邻近组织相比，成纤维细胞灶中pRB的表达减少，而p27的表达没有变化。该结果表明成纤维细胞灶中 pRB 的下调有助于 IPF 的发病机制。

项目成果

Th1/Th2 profile in peripheral blood in atopic cough and atopic asthma

• DOI: 10.1046/j.1365-2222.2003.01578.x
• 发表时间: 2003-01-01
• 期刊: CLINICAL AND EXPERIMENTAL ALLERGY
• 影响因子: 6.1
• 作者: Shirai, T;Suzuki, K;Nakamura, H
• 通讯作者: Nakamura, H

Enhanced Mdn2 activity inhibits PRB function in ubiquitin-dependent degradation

增强的 Mdn2 活性抑制泛素依赖性降解中的 PRB 功能

• 发表时间: 2004
• 期刊: EMBO J 30
• 作者: Uchida;C et al.
• 通讯作者: C et al.

Limitations of corticosteroids and cytotoxic agents in treating idiopathic pulmonary fibrosis

皮质类固醇和细胞毒药物治疗特发性肺纤维化的局限性

• 发表时间: 2003
• 期刊: Jn Med Assoc J 46
• 作者: Nakamura Y;Chida K;et al.;Chida K
• 通讯作者: Chida K

Asada K, Chida K, et al.: "Anti-inflammatory roles of peroxisome proliferator-activated receptor γ in human alveolar macrophages"Am J Respir Crit Care Med. 169. 195-200 (2004)

Asada K、Chida K 等：“人肺泡巨噬细胞中过氧化物酶体增殖物激活受体 γ 的抗炎作用”Am J Respir Crit Care Med 169. 195-200 (2004)

High-dose intravenous glucocorticoid therapy abrogates circulating dendritic cells

高剂量静脉注射糖皮质激素治疗消除循环树突状细胞

• 发表时间: 2003
• 期刊: J Allergy Clin Immunol 112
• 作者: Suda T;Chida K;et al.
• 通讯作者: et al.