| Project/Area Number |
11670576
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
HAYASHI Seiji Graduate School of Medicine, Osaka University Lecturer, 医学系研究科, 講師 (70218577)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | 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(NSIP) / 過形成 / IPF / TGF-β受容体 / 遺伝子変異 |
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| Research Abstract |
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.
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