2011 Fiscal Year Final Research Report
Functional analysis of tetraspanins(CD9, CD151) in lung fibrosis
| Project/Area Number |
21590992
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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 |
TAKEDA Yoshito 大阪大学, 医学系・研究科, 助教 (40452388)
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| Co-Investigator(Kenkyū-buntansha) |
TACHIBANA Isao 大阪大学, 医学系・研究科, 講師 (60324761)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 特発性肺線維症 / テトラスパニン / インテグリン、CD9 / CD151 |
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| Research Abstract |
Pulmonary fibrosis(PF) is the process whereby excess fibrous connective tissue forms and characterized by the accumulation of fibrillar collagen. Tetraspanins, key partners of integrins, facilitate the formation of multiple molecular complexes and regulate cell function. We previously reported double deletion of tetraspanin CD9 and CD81 in mice spontaneously developed COPD-like phenotype. The gene functions analyses from DNA Microarray unexpectedly revealed that' connective tissue development and function' were ranked high in CD151 KO lungs. Notably, CD151 KO mice spontaneously developed lung fibrosis with age. Consistently, the level of p-Smad2 in the CD151 KO mice was augmented in the whole lung and in the epithelium. Indeed, deletion of CD151 in alveolar epithelial cells leads to increased p-Smad2 activity on Matrigel, and mesenchymal-like changes. Of interest, expression of CD151 in epithelial cells from IPF patients was downregulated compared with that of healthy controls. Given that CD151 plays a pivotal role to prevent fibrosis through maintaining epithelial integrity, CD151 could be a novel target for PF.
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