Microsatellite Instability in Transforming Growth Factor - Betal Type II Receptor Gene in Alveolar Lining Epithelial Cells of Idiopathic Pulmonary Fibrosis

特发性肺纤维化肺泡衬里上皮细胞转化生长因子-βII型受体基因的微卫星不稳定性

• 批准号: 11670576
• 负责人: HAYASHI Seiji
• 金额: $ 2.3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670576/
• 关键词: Idiopathic pulmonary fibrosis; Alveolar epithelial cell; Transforming growth factor-β; type II receptor; Microsatellite Instability; non-specific interstitial pneumonia; 肺癌; transforming growth factor(TGF)-β; non-specific interstitial pneumonia(NS

It has been reported that transforming growth factor (TGF)-β, which plays an integral role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). On the assumption that the hyperplastic alveolar lining epithelial cells (ALECs) which are characteristic pathologic features of IPF, have escaped from the growth inhibitory effects of TGF-β, we searched for mutations in the microsatellite of the TGF-β receptor type II (TβRII) gene. To detect a deletion in the polyadenine tract in exon 3 of the TβRII gene, cells were isolated by microdissection from lung sections of IPF patients, and DNA was extracted from these cells and amplified by high fidelity PCR.A total of 121 sites of hyperplastic ALECs from 11 IPF patients were analyzed, and a one-base-pair deletion was detected in 9 sites from 5 patients. The mutation was also detected in smooth muscle-like cells of the thickened pulmonary artery. In some tissue areas where the deletion was detected, low TβRII expression was confirmed by immunohistochemical staining. In non-specific interstitial pneumonia (NSIP), we also detected the deletion in the TβRII gene in one case of NSIP out of two. These data suggest that microsatellite instability in the TβRII gene occurred in some lesions of hyperplastic ALECs in IPF, although at a low incidence, and this genetic disorder might play a partial role in the pathologic changes of pulmonary fibrosis including IPF.

已有研究表明，转化生长因子-β在特发性肺纤维化的发病机制中起着不可或缺的作用。假设肺间质纤维化特有的病理特征--肺泡衬里上皮细胞(ALECs)已逃脱转化生长因子-β的生长抑制作用，我们寻找转化生长因子-β受体II型(T-βRII)基因微卫星的突变。为检测T-βRII基因外显子3多聚腺苷束的缺失，采用显微切片法分离肺间质纤维化患者肺组织细胞，提取细胞DNA，用高保真聚合酶链式反应进行扩增。对11例肺间质纤维化患者的12 1个增生性肺泡细胞进行分析，发现5例患者9个碱基对缺失。在增厚的肺动脉中也检测到这种突变。在检测到缺失的部分组织中，免疫组织化学染色证实TβRII低表达。在非特异性间质性肺炎中，我们还检测到两例中有一例TβRII基因缺失。提示T-βRII基因微卫星不稳定性在肺纤维化包括肺纤维化的肺纤维化的病理改变中可能起部分作用。

项目成果

Masahide Mori, Hiroshi Kida, Hiroshi Morishita, Sho Goya, Hiroto Matsuoka, Toru Arai, Tadashi Osaki, Isao Tachibana, Masami Ito, Takeshi Ogura and Seiji Hayashi: "Microsatellite Instability in Transforming Growth Factor - Betal Type II Receptor Gene in Al

Masahide Mori、Hiroshi Kida、Hiroshi Morishita、Sho Goya、Hiroto Matsuoka、Toru Arai、Tadashi Osaki、Isao Tachibana、Masami Ito、Takeshi Ogura 和 Seiji Hayashi：“Al 中转化生长因子 - Betal II 型受体基因的微卫星不稳定性

Masahide Mori et.al.: "Microsatellite Instability in Transforming Growth Factor-Beta1 Type II Receptor Gene in Alveolar Lining Epithelial Cells of Idiopathic Pulmonary Fibrosis."Am J Respir Cell Mol Biol. (in press). (2001)

Masahide Mori 等人：“特发性肺纤维化肺泡衬里上皮细胞中转化生长因子-Beta1 II 型受体基因的微卫星不稳定性。”Am J Respir Cell Mol Biol。

Toru Arai: "Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo"Am J Physiol. (in press). (2000)

Toru Arai：“将白细胞介素 10 基因引入小鼠体内可抑制博莱霉素诱导的体内肺损伤”Am J Physiol。

Mitsuhiro Yoshida, Junko Sakuma-Mochizuki, Kin'ya Abe, Toru Arai, Masahide Mori, Sho Goya, Hiroto Matsuoka, Seiji Hayashi, Yasufumi Kaneda, and Tadamitsu Kishimoto.: "In vivo gene transfer of an extracellular domain of platelet-derived growth factor beta

Mitsuhiro Yoshida、Junko Sakuma-Mochizuki、Kinya Abe、Toru Arai、Masahide Mori、Sho Goya、Hiroto Matsuoka、Seiji Hayashi、Yasufumi Kaneda 和 Tadamitsu Kishimoto。：“血小板衍生生长的细胞外域的体内基因转移

Masahide Mori et.al.: "Microsatellite Instability in Transforming Growth Factor - Betal Type II Receptor Gene in Alveolar Lining Epithelial Cells of Idiopathic Pulmonary Fibrosis."Am J Respir Cell Mol Biol. (in press). (2001)

Masahide Mori 等人：“特发性肺纤维化肺泡衬里上皮细胞中转化生长因子 - Betal II 型受体基因的微卫星不稳定性。”Am J Respir Cell Mol Biol。