2023 Fiscal Year Final Research Report
Elucidation of a novel pulmonary fibrosis mechanism based on periostin and construction of a new therapeutic strategy for interstitial pneumonia
| Project/Area Number |
21K08182
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Saga University |
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Principal Investigator |
Nanri Yasuhiro (宮内康弘) 佐賀大学, 医学部, 助教 (00382218)
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| Co-Investigator(Kenkyū-buntansha) |
出原 賢治 佐賀大学, 医学部, 教授 (00270463)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | ペリオスチン / SOX11 / 強皮症 / 間質性肺炎 |
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| Outline of Final Research Achievements |
Periostin is a matricellular protein playing a key role in the generation of fibrosis by amplifying the TGF-b signals. SOX11 is a transcription factor playing several important roles in organ development in embryos. We have shown that SOX11 induces periostin expression. However, the roles of the interactions among the TGF-b signals, periostin, and SOX11 remain unknown in the pathogenesis of SSc. In this study, we found that dermal fibroblasts derived from SSc patients showed constitutive, high expression of SOX11, which is significantly induced by TGF-b. SOX11 forms a positive loop with periostin to activate the TGF-b signals in SSc dermal fibroblasts. Genetic deletion of Sox11 in fibroblasts impairs dermal fibrosis. Moreover, using the DNA microarray, we identified several fibrotic factors dependent on the TGF-b/SOX11/periostin pathway. Our findings show that a positive loop formed by SOX11 and periostin in fibroblasts upregulates the TGF-b signals, leading to skin fibrosis.
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| Free Research Field |
線維化疾患
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| Academic Significance and Societal Importance of the Research Achievements |
間質性肺炎は肺組織での不可逆的な線維化を伴い予後も極めて悪く、新しい治療薬の開発が求められている。我々は、マトリセルラータンパク質の一つであるペ リオスチンが、肺線維化の形成に重要な役割を果たしていることを世界に先駆けて明らかにしてきた。また、最近、転写因子の一つであるSOX11がペリオスチンの発現を誘導し、肺や皮膚線維化に関与していることを証明した。
今回、我々の同定したSOX11/ペリオスチンのフィードバックループを阻害することが出来れば、特定の線維化シグナルを阻害するので、IPF、SScの新たな治療戦略として期待される。
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