新しい抗利尿ホルモンが腫瘍誘発性腎機能障害を制御する
Wenhao Xu1,2, Gerui Li1, Yuan Chen1,2
1Department of Geriatrics, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, Hubei, China.
Nature
|December 6, 2023
まとめ
腫瘍は 液体の排泄を阻害するホルモンを放出することで 腎臓の機能を損なう可能性があります このホルモンの経路を 癌のマウスで遮断することで 腎臓の機能不全が軽減され 新しい治療戦略が生まれました
科学分野:
- 比較生理学
- 分子内分泌学
- 癌の生物学
背景:
- 腎臓の機能と流体輸送は,生理学的および病理学的状態への適応に不可欠です.
- ヒトの悪性腫瘍は,化学療法や炎症による腎機能不全や小尿症を引き起こすことが多い.
- 腫瘍が腎機能を調節する直接的なメカニズムはほとんど不明です.
研究 の 目的:
- 腫瘍が腎機能を調節する直接的なメカニズムを調査する.
- 腫瘍と腎臓の交響に 関わる新しい経路を特定するために
- 癌に関連した腎機能障害の治療目標を探求する.
主な方法:
- ドロソフィラ・メラノガスターの保存された腫瘍モデルを使用した.
- 腫瘍細胞によって分泌されるイオン輸送ペプチドイソフォームF (ITP_F) の役割を特徴づけた.
- TkR99D,酸化窒素合成体,cGMPを含むシグナル伝達経路を調査した.
- ネズミのがんモデルにおけるニューロキニン3受容体 (NK3R) 阻害の効果を調べた.
主要な成果:
- ITP_Fは,腸内腫瘍細胞によって分泌される,フライの抗尿ホルモンである.
- 腫瘍に由来するITP_Fが 腎臓機能を損なうことが示され, 液体の蓄積を引き起こします.
- ITP_Fはマルピギウム管の星状細胞のTkR99Dを標的とし,酸化窒素合成酵素-cGMPの信号伝達を活性化し,液体の排泄を抑制することを示した.
- 哺乳類NK3Rの抗利尿作用が確認され,NK3Rの阻害が腫瘍を持つマウスの腎機能不全を緩和することを示した.
結論:
- 腫瘍と腎臓の交響を媒介する 新種の抗尿経路を発見した
- 腫瘍によって分泌されるITP_ Fは,液体の排泄を阻害することによって,直接腎機能を損なう.
- 哺乳類のNK3RはハエのTkR99Dの機能的な同型であり,がんに関連した腎機能障害の潜在的な治療標的である.
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