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

Research output: Contribution to journalArticle

207 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 languageEnglish
Pages (from-to)57-62
Number of pages6
JournalNature
Volume519
Issue number7541
DOIs
Publication statusPublished - Mar 5 2015

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Regeneration
Inflammation
Interleukin-6 Receptors
src-Family Kinases
Inflammatory Bowel Diseases
Colorectal Neoplasms
Interleukin-6
Epithelial Cells
Cell Proliferation
Cytokines
Wounds and Injuries
Growth

All Science Journal Classification (ASJC) codes

  • General

Cite this

Taniguchi, K., Wu, L. W., Grivennikov, S. I., De Jong, P. R., Lian, I., Yu, F. X., ... Karin, M. (2015). A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature, 519(7541), 57-62. https://doi.org/10.1038/nature14228

A gp130-Src-YAP module links inflammation to epithelial regeneration. / Taniguchi, Koji; Wu, Li Wha; Grivennikov, Sergei I.; De Jong, Petrus R.; Lian, Ian; Yu, Fa Xing; Wang, Kepeng; Ho, Samuel B.; Boland, Brigid S.; Chang, John T.; Sandborn, William J.; Hardiman, Gary; Raz, Eyal; Maehara, Yoshihiko; Yoshimura, Akihiko; Zucman-Rossi, Jessica; Guan, Kun Liang; Karin, Michael.

In: Nature, Vol. 519, No. 7541, 05.03.2015, p. 57-62.

Research output: Contribution to journalArticle

Taniguchi, K, Wu, LW, Grivennikov, SI, De Jong, PR, Lian, I, Yu, FX, Wang, K, Ho, SB, Boland, BS, Chang, JT, Sandborn, WJ, Hardiman, G, Raz, E, Maehara, Y, Yoshimura, A, Zucman-Rossi, J, Guan, KL & Karin, M 2015, 'A gp130-Src-YAP module links inflammation to epithelial regeneration', Nature, vol. 519, no. 7541, pp. 57-62. https://doi.org/10.1038/nature14228
Taniguchi K, Wu LW, Grivennikov SI, De Jong PR, Lian I, Yu FX et al. A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature. 2015 Mar 5;519(7541):57-62. https://doi.org/10.1038/nature14228
Taniguchi, Koji ; Wu, Li Wha ; Grivennikov, Sergei I. ; De Jong, Petrus R. ; Lian, Ian ; Yu, Fa Xing ; Wang, Kepeng ; Ho, Samuel B. ; Boland, Brigid S. ; Chang, John T. ; Sandborn, William J. ; Hardiman, Gary ; Raz, Eyal ; Maehara, Yoshihiko ; Yoshimura, Akihiko ; Zucman-Rossi, Jessica ; Guan, Kun Liang ; Karin, Michael. / A gp130-Src-YAP module links inflammation to epithelial regeneration. In: Nature. 2015 ; Vol. 519, No. 7541. pp. 57-62.
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