gp130-Src-YAPモジュールは,炎症と上皮細胞再生を結びつけています

Koji Taniguchi¹, Li-Wha Wu², Sergei I Grivennikov³

¹1] Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA [2] Departments of Pharmacology and Pathology, University of California, San Diego, La Jolla, California 92093, USA [3] Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan [4] Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.

Nature

|March 4, 2015

まとめ

gp130経由のインタールイウキン-6 (IL-6) ファミリーシグナル伝達は,YAPとNotch経路を活性化し,STAT3.3とは独立して組織再生と治癒を促進します. このメカニズムは,損傷後の腸の修復に不可欠です.

科学分野:

細胞生物学細胞生物学
分子生物学は分子生物学である.
免疫学免疫学とは

背景:

炎症は組織再生に重要な役割を果たしますが,その基礎となる分子機構は完全に理解されていません.
インタールユーキン-6 (IL-6) 家族は,炎症および再生プロセスに関与し,炎症性腸疾患や結腸直腸がんなどの疾患において上位調節されます.

研究の目的:

組織再生におけるIL-6サイトカインの共受容体であるgp130の役割を明らかにする.
組織修復と疾患の文脈でgp130によって活性化されたシグナル伝達経路を調査する.

主な方法:

実験はマウスモデルとヒトの細胞系を用いて行われました.
転写レギュレータYAPとNotchの活性化を調査した.
gp130のチロシンキナーゼSrcとYesとの関連性を分析した.

主要な成果:

YAPとNotchのgp130活性化は,上皮細胞の増殖を促進し,STAT3.3とは独立して,粘膜の侵食に対する耐性を授与する.
gp130シグナリングは,SrcとYesキナーゼを介してYAPのリン酸化,安定化,核転位を刺激する.
このシグナリングモジュールは,粘膜の損傷時に活性化され,治癒を促進し,腸の障壁機能を維持します.

結論:

YAPとNotchによるgp130媒介信号伝達は,組織再生と腸内修復の重要な経路である.
このメカニズムを理解することで,炎症性疾患や癌の潜在的治療標的の洞察が得られます.

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