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.

据报道，转化生长因子（TGF）-β在特发性肺纤维化（IPF）中起着不可或缺的作用。假设是IPF的特征性病理特征的增生性肺泡衬里上皮细胞（ALEC）已从TGF-β的生长抑制作用中逃脱，我们在TGF-β受体II型（TβRII）基因的TGF-β受体受体的微磷灰石中搜索了突变。为了检测TβRII基因外显子3中的多腺苷道中缺失，通过从IPF患者的肺切片中进行显微解剖分离细胞，并从这些细胞中提取DNA，并通过高保真性PCR.A总共从111名IPF患者的增生性ALEC的位点进行扩增，从11个ipf患者中进行了一个分析，并从11次分析了一个basese delet and-basese delet andion and-basese delet。在增厚的肺动脉的平滑肌样细胞中也检测到突变。某些发现缺失的组织区域，通过免疫组织化学染色证实了低TβRII表达。在非特异性间质肺炎（NSIP）中，我们还检测到两种NSIP的一个情况下的TβRII基因中的缺失。这些数据表明，TβRII基因中的微卫星不稳定性发生在IPF中的一些增生性ALEC病变中，尽管在低入射率下，这种遗传疾病可能在包括IPF在内的肺纤维化的病理变化中起部分作用。

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

Junko Sakuma-Mochizuki: "Changes in pulmonary histology and exfoliated bronchoalveolar cells induced by in vivo introduction of the tumor necrosis factor-a gene"Inflammation. 24. 11-19 (2000)

Junko Sakuma-Mochizuki：“体内引入肿瘤坏死因子-a基因诱导的肺组织学和脱落支气管肺泡细胞的变化”炎症。