エピデルマ・成長因子受容体の活性化は,損傷した腎臓近辺管の上皮細胞におけるSOX9の発現を刺激する
Jianchun Chen1,2,3, Fenfen Peng2,3, Mengdi Jiang2,3
1Department of Veterans Affairs, Nashville, Tennessee.
Journal of the American Society of Nephrology : JASN
|September 2, 2025
まとめ
急性腎臓損傷 (AKI) の後の腎臓近辺管細胞におけるSOX9誘発には,表皮成長因子受容体 (EGFR) の活性化が不可欠である. このメカニズムは,腎臓の修復と慢性腎臓病 (CKD) の発症を理解するための鍵です.
科学分野:
- 腎臓科
- 分子生物学
- 細胞生物学
背景:
- SOX9の発現は急性腎損傷後の腎修復に不可欠である.
- RPTCにおける持続的なSOX9上昇は慢性腎疾患 (CKD) の発症と関連しています.
- 腎臓損傷によるSOX9誘導のメカニズムについては,さらなる解明が必要である.
研究 の 目的:
- 損傷したRPTCにおけるSOX9発現の調節における表皮成長因子受容体 (EGFR) の作用を調査する.
- 腎臓損傷の文脈でEGFR活性化とSOX9誘導を結びつける分子経路を解明する.
主な方法:
- SOX9とEGFRの発現は,急性管状損傷と慢性アロ移植腎不全の患者からのヒト腎管状上皮細胞で調べられた.
- EGFRチロシンキナーゼ欠乏マウスを含むマウスモデルを使用して,SOX9のアップレギュレーションにおけるEGFRの役割を研究した.
- SOX9に対するEGFRの効果を確認するために,培養されたヒトRPTCにおけるメカニズムを調査した.
主要な成果:
- SOX9とEGFRの発現の上昇と局所化がヒトの腎管状上皮細胞で観察された.
- RPTCにおけるhHB- EGFの過剰発現はSOX9を増加させ,EGFR欠乏したマウスではその効果は消滅した.
- EGFR阻害 (遺伝的または薬学的) は,不全性AKI後のSOX9発現を減少させた.
- 発血性AKIは近接管のEGFRを活性化させ,Akt- YAP/ TAZ- TEAD経路とSOX9誘導を開始する.
結論:
- EGFRの活性化は,AKI後のRPTCにおけるSOX9発現の重要な調節因子である.
- EGFR-Akt-YAP/TAZ-TEAD信号軸は,腎臓損傷に対する反応としてSOX9誘導を媒介する.
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