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ErbB3は,低酸素誘発性肺高血圧における内皮機能障害を制御する

Jin-Song Bian^1,2, Jingyu Chen³, Junting Zhang¹

¹Key Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People's Hospital (the First Affiliated Hospital, Southern University of Science and Technology; the Second Clinical Medical College, Jinan University), China (J.-S.B., J.Z., Y.L., R.C., X.N.).

|January 12, 2024

まとめ

ErbB3は肺高血圧 (PH) で上調され,疾患の進行を促します. ErbB3をMM-121で標的にすることは,PH治療の治療的可能性を示しています.

科学分野:

心血管研究
細胞生物学
分子医学

背景:

肺高血圧 (PH) は血管の改造と肺動脈内皮細胞機能不全を伴う.
ErbB3 (ヒト表皮成長因子受容体3) は,細胞プロセスに関与する受容体チロシンキナーゼである.
現在のPH療法は治療の選択肢が不足しており,新しい治療目標の必要性を強調しています.

研究の目的:

肺高血圧におけるErbB3の病理的役割を調査する.
ErbB3をPHの潜在的なバイオマーカーと治療標的として評価する.

主な方法:

ErbB3発現を分析するために,マイクロアレイ,免疫光,およびウエスタン・ブロッティングを使用した.
ErbB3の遺伝子操作 (過剰発現,デリート,ノックダウン) を伴うPHのネズミモデルを使用した.
人体細胞におけるYB-1と低酸素誘導因子を含む下流メカニズムを調査した.

主要な成果:

ErbB3はPH患者の血清,肺,肺動脈内皮細胞で有意に上昇した.
ErbB3の過剰発現はPH現象を悪化させ,ErbB3の削除/ノックダウンは改善した.
新しいErbB3-YB-1-HIF1αシグナル伝達経路とErbB3-periostin-HIF1α陽性フィードバックループを特定した.
抗ErbB3抗体MM-121は,低酸素誘発PHモデルで予防効果と治療効果を示した.

結論:

ErbB3は肺高血圧の病原性における重要な媒介体である.
ErbB3はPHに対する新しい有望な治療目標です.
MM-121はPHの治療に大きな可能性を秘めている.

キーワード:

マウスのErbB3タンパク質マウスのYB-1タンパク質細胞増殖内皮細胞肺高血圧ペリオスティン

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