肺高血圧および慢性閉塞性肺疾患を予防するために,心肺原細胞におけるSuv4-20h1による表遺伝子調節が必要である

Hui Qi¹, Hang Liu¹, Soni Savai Pullamsetti²

¹Department of Cardiac Development and Remodeling (H.Q., H.L., S.G., C.K., A.A., Y.Z., X.Y., T.B.), Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.

Circulation

|July 12, 2021

まとめ

ヒストン変容体SUV4-20H1は心肺発達に不可欠です. その喪失は,マウスの慢性閉塞性肺疾患 (COPD) 様および肺高血圧 (PH) 様現象を引き起こし,新しい治療標的を明らかにする.

科学分野:

エピジェネティクス
分子生物学
心肺医学

背景:

肺高血圧 (PH) と慢性閉塞性肺疾患 (COPD) の病原性には複雑な環境的および遺伝的要因が含まれています.
発達の異常や表遺伝子異常は,PHとCOPDの傾向に関わっているが,十分に理解されていない.

研究の目的:

PHとCOPDに関連した肺組織における表遺伝的変化を特定する.
ヒストン改変H4K20me2/3とその関連酵素SUV4-20H1の肺病原性における役割を調査する.

主な方法:

ヒトのPHとCOPD患者群で,免疫光を用いてヒストンの変化をスクリーニングする.
心肺原細胞と特定の細胞タイプを標的とした Suv4-20h1 ノックアウトマウスモデルの開発.
Suv4-20h1の機能を分析するために,血液動力学研究,形態測定分析,および分子/細胞技術を使用する.

主要な成果:

ヒトのCOPD患者で観察されたH4K20me2/ 3の濃度の低下は,SUV4 - 20H1の活性に関連している.
ネズミのSuv4 - 20h1の喪失は,リンパ性組織形成,多発性,および血管欠陥を含むCOPDのような/PHフェノタイプを誘発した.
SUV4-20H1はSOD3遺伝子の発現を抑制し,SOD3が変異体で増加すると,過酸化水素が蓄積され,血管および膜の欠陥が生じます.

結論:

SUV4-20H1は心臓肺疾患の発達に重要な役割を果たし,表遺伝的調節と疾患の起源を結びつけています.
発見はPHとCOPDの病原性メカニズムへの洞察を提供します.
心肺疾患の新たなエピジェネティック療法の開発の可能性

キーワード:

マウスのSUV4-20H1タンパク質アルベオール,肺肺高血圧酸化減少肺疾患慢性閉塞性スーパーオキシードジスミュータゼ3

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