Elucudating TGFbeta-BMP Signaling Disruption and Vascular Anomalies.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07430
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Itoh Fumiko 東京薬科大学, 生命科学部, 准教授 (70502582)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: TGF-β / 血管新生 / がん転移 / がん悪液質 / BMP / ミオスタチン

Outline of Final Research Achievements

The analysis of this genetically modified mice, which exhibits endothelial cell-specific BMP signaling deficiency, had the potential to provide valuable insights into the mechanism of pulmonary hypertension development and the development of therapeutic drugs. Furthermore, it has been revealed that TGF-β, which also acts as a factor in cancer progression, affects tumor vascular endothelial cells and lymphatic endothelial cells, promoting metastasis. Inhibiting TGF-β in endothelial cells is believed to contribute to the development of therapeutic drugs that can suppress cancer metastasis. Additionally, the development of a TGF-β family member, myostatin, inhibitory peptide has shown effective muscle-enhancing effects. Particularly, in cancer cachexia model mice, it showed that increasing food intake and preventing muscle wasting are crucial aspects of treatment.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

肺動脈性肺高血圧症は予後不良の難病である。本研究で作成した遺伝子改変マウスは有望な肺高血圧症のモデルマウスと考えられ、今後の病態発症メカニズム解明や治療薬開発に役立つ可能性が高い。さらに、TGF-βシグナルは様々な側面で悪性的に働くことが示され、その阻害剤の開発は腫瘍転移抑制につながる可能性が高い。
開発したミオスタチン阻害ペプチド・MID-35はアナモレリンとの併用治療により食餌摂取量と筋肉消耗を効果的に改善できることを見出した。がん悪液質患者の治療において食事摂取量増加と筋肉消耗阻害が治療ポイントになると期待される。