人間の潰瘍性大腸炎の遺伝子の変異
Kosaku Nanki1,2, Masayuki Fujii1,3, Mariko Shimokawa1
1Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan.
Nature
|December 20, 2019
まとめ
組織が老化すると がん変異が蓄積されます 潰瘍性大腸炎患者では,大腸細胞がIL-17シグナル遺伝子の変異を起こし,潜在的に炎症と病気を引き起こします.
科学分野:
- 胃腸内科
- 遺伝学
- 免疫学
背景:
- 老化した組織は癌変異を持つ体内クローンを蓄積する.
- ヒトの非新形成性腸のクローナル膨張は十分に理解されていません.
- 潰瘍性大腸炎は慢性的な腸炎を伴う
研究 の 目的:
- 潰瘍性大腸炎患者の大腸内皮質における体内変異を調査する.
- 炎症した結腸の変異が機能上の利点をもたらすかどうかを判断する.
- 体内の突然変異と潰瘍性大腸炎の病原性との関係を調べる.
主な方法:
- 76人のヒト大腸器官の全エクソームシーケンシング
- 標的の配列化により 変異の拡散が確認される
- CRISPRベースのノックアウトスクリーニング
主要な成果:
- 潰瘍性大腸炎の 独特の変異パターンを特定した
- IL-17シグナル伝達経路の遺伝子 (NFKBIZ,ZC3H12A,PIGR) に変異が見つかりました.
- 変異はIL-17A誘発のアポトーシスに耐性をもたらした.
結論:
- 人間の大腸の表皮における体内変異は炎症と関連している.
- 変異は,潰瘍性大腸炎の敵対的なマイクロ環境で生存を促進する可能性があります.
- この遺伝的適応は潰瘍性大腸炎の病原化に寄与する可能性があります.
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