A gp130-Src-YAP module links inflammation to epithelial regeneration

Koji Taniguchi; Li Wha Wu; Sergei I. Grivennikov; Petrus R. De Jong; Ian Lian; Fa Xing Yu; Kepeng Wang; Samuel B. Ho; Brigid S. Boland; John T. Chang; William J. Sandborn; Gary Hardiman; Eyal Raz; Yoshihiko Maehara; Akihiko Yoshimura; Jessica Zucman-Rossi; Kun Liang Guan; Michael Karin

doi:10.1038/nature14228

A gp130-Src-YAP module links inflammation to epithelial regeneration

Koji Taniguchi, Li Wha Wu, Sergei I. Grivennikov, Petrus R. De Jong, Ian Lian, Fa Xing Yu, Kepeng Wang, Samuel B. Ho, Brigid S. Boland, John T. Chang, William J. Sandborn, Gary Hardiman, Eyal Raz, Yoshihiko Maehara, Akihiko Yoshimura, Jessica Zucman-Rossi, Kun Liang Guan, Michael Karin

Institute of Molecular Medicine

Research output: Contribution to journal › Article › peer-review

518 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	57-62
Number of pages	6
Journal	Nature
Volume	519
Issue number	7541
DOIs	https://doi.org/10.1038/nature14228
Publication status	Published - 2015 Mar 5

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Taniguchi, K., Wu, L. W., Grivennikov, S. I., De Jong, P. R., Lian, I., Yu, F. X., Wang, K., Ho, S. B., Boland, B. S., Chang, J. T., Sandborn, W. J., Hardiman, G., Raz, E., Maehara, Y., Yoshimura, A., Zucman-Rossi, J., Guan, K. L., & Karin, M. (2015). A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature, 519(7541), 57-62. https://doi.org/10.1038/nature14228

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abstract = "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.",

author = "Koji Taniguchi and Wu, {Li Wha} and Grivennikov, {Sergei I.} and {De Jong}, {Petrus R.} and Ian Lian and Yu, {Fa Xing} and Kepeng Wang and Ho, {Samuel B.} and Boland, {Brigid S.} and Chang, {John T.} and Sandborn, {William J.} and Gary Hardiman and Eyal Raz and Yoshihiko Maehara and Akihiko Yoshimura and Jessica Zucman-Rossi and Guan, {Kun Liang} and Michael Karin",

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AU - Taniguchi, Koji

AU - Wu, Li Wha

AU - Grivennikov, Sergei I.

AU - De Jong, Petrus R.

AU - Lian, Ian

AU - Yu, Fa Xing

AU - Wang, Kepeng

AU - Ho, Samuel B.

AU - Boland, Brigid S.

AU - Chang, John T.

AU - Sandborn, William J.

AU - Hardiman, Gary

AU - Raz, Eyal

AU - Maehara, Yoshihiko

AU - Yoshimura, Akihiko

AU - Zucman-Rossi, Jessica

AU - Guan, Kun Liang

AU - Karin, Michael

PY - 2015/3/5

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AB - 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.

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A gp130-Src-YAP module links inflammation to epithelial regeneration

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