NR5A2による転写調節は,臓の分化と炎症と関連している
Isidoro Cobo1, Paola Martinelli1, Marta Flández1
1Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre-CNIO, Madrid, Spain.
Nature
|February 15, 2018
まとめ
孤児核受容体NR5A2は通常,臓の炎症を抑制する. ネズミとヒトのNR5A2発現が低下すると,炎症前状態になり,臓がんのリスクが高まります.
科学分野:
- 分子生物学
- 腫瘍学
- 胃腸内科
背景:
- 慢性炎症は様々な癌の危険因子として知られています.
- 炎症と細胞の分化を制御するトランスクリプションネットワークは異なると考えられていた.
- 孤児核受容体NR5A2は,複数の代謝および発達プロセスに関与しています.
研究 の 目的:
- 臓の炎症と癌におけるNR5A2の役割を調査する.
- NR5A2の細胞分化と 臓の炎症性遺伝子ネットワークの関係を調べる
主な方法:
- ヘテロジゴスなNr5a2欠乏症 (Nr5a2+/-) を有するマウスにおける全体的なトランスクリプトミックの分析
- NR5A2 mRNA発現が低下したヒトの臓組織との比較
- 観察されたフェノタイプにおけるAP-1転写因子とJunの役割を調査した.
主要な成果:
- Nr5a2+/-マウスは,上皮細胞自律的基礎前炎症状態を示しています.
- この炎症前状態は,NR5A2の発現が低下したヒトの臓に保存されます.
- NR5A2は差異化から炎症性遺伝子にシフトし,AP-1-依存の転写を促進します.
- 炎症前フェノタイプと 欠陥のある再生を救います
結論:
- 臓の分化特有の転写ネットワークも炎症プログラムを抑制する.
- NR5A2発現の減少はこれらのネットワークを破壊し,炎症を助長し,潜在的に臓がんのリスクを増やす可能性があります.
- NR5A2は,分化と炎症のバランスをとることで,臓の恒常性を維持する上で重要な役割を果たします.
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