一个 gp130-Src-YAP 模块将炎症与上皮再生联系起来。
A gp130-Src-YAP module links inflammation to epithelial regeneration.
机构信息
1] 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.
1] Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA [2] Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
出版信息
Nature. 2015 Mar 5;519(7541):57-62. doi: 10.1038/nature14228. Epub 2015 Feb 25.
Inflammation promotes regeneration of injured tissues through poorly understood mechanisms, some of which involve interleukin (IL)-6 family members, the expression of which is elevated in many diseases including inflammatory bowel diseases and colorectal cancer. Here we show in mice and human cells that gp130, a co-receptor for IL-6 cytokines, triggers activation of YAP and Notch, transcriptional regulators that control tissue growth and regeneration, independently of the gp130 effector STAT3. Through YAP and Notch, intestinal gp130 signalling stimulates epithelial cell proliferation, causes aberrant differentiation and confers resistance to mucosal erosion. gp130 associates with the related tyrosine kinases Src and Yes, which are activated on receptor engagement to phosphorylate YAP and induce its stabilization and nuclear translocation. This signalling module is strongly activated upon mucosal injury to promote healing and maintain barrier function.
炎症通过尚未完全阐明的机制促进受损组织的再生，其中一些机制涉及白细胞介素 (IL)-6 家族成员，其表达在许多疾病中升高，包括炎症性肠病和结直肠癌。在这里，我们在小鼠和人类细胞中表明，gp130 是 IL-6 细胞因子的共受体，可独立于 gp130 效应物 STAT3 触发 YAP 和 Notch 的激活，Notch 是控制组织生长和再生的转录调节剂。通过 YAP 和 Notch，肠道 gp130 信号刺激上皮细胞增殖，导致异常分化并赋予对黏膜侵蚀的抵抗力。gp130 与相关的酪氨酸激酶Src 和 Yes 结合，在受体结合时被激活，磷酸化 YAP 并诱导其稳定和核转位。这种信号模块在黏膜损伤时被强烈激活，以促进愈合并维持屏障功能。
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