A gp130–Src–YAP module links inflammation to epithelial regeneration
Open accessAbstract
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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Interleukin-6 is an endurance-exercise-related signal linked to YAP/TAZ.
“Endurance exercise-associated signals linked to YAP/TAZ”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as Taniguchi et al Nature (2015)
The Discussion identifies IL-6 as an activator of the gp130–Src–YAP pathway, supporting a link to YAP. The paper discusses inflammation and epithelial regeneration, not endurance exercise; it does not establish that IL-6 is an endurance-exercise-associated signal. No page numbers are available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredInterleukin-6 activates Yap through the gp130 co-receptor in the intestine.
“Recently, interleukin-6 has been shown to activate Yap through the gp130 co-receptor in the intestine (125).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [125]
IL-6 activates STAT3 and induces YAP activation through SRC family kinases.
“IL-6 activates STAT3, induces Yes-associated protein (YAP) activation through SRC family kinases”
From Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2 (2022) · cites this paper as [45]
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- Authors
- 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.
- Affiliations
- Kyushu University (JP)
- University of California San Diego (US)
- Fox Chase Cancer Center (US)
- Lamar University (US)
- Fudan University (CN)
- VA San Diego Healthcare System (US)
- Medical University of South Carolina (US)
- Keio University (JP)
- Corresponding author
- Karin, Michael
- ORCID
- Venue
- Nature
- Published
- 2015-02-25
- Volume
- 519
- Issue
- 7541
- Pages
- 57-62
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4447318
- OpenAlex
- W2072304718
- Cited by
- 633
- References
- 60
- Citations by year
- 2026: 35 · 2025: 39 · 2024: 36 · 2023: 59 · 2022: 79 · 2021: 67 · 2020: 81 · 2019: 51 · 2018: 62 · 2017: 43 · 2016: 55 · 2015: 22
- FWCI
- 26.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Crohn's and Colitis Foundation
- National Institutes of Health (1dp2od008469-01)
- Japan Society for the Promotion of Science (24390321, 25221305, 25670234)
- National Eye Institute (R01EY022611, EY022611)
- National Cancer Institute (R01CA118165, CA132809, CA118165-09, R01CA132809)
- National Institute of Allergy and Infectious Diseases (R01AI095277)
- National Institute of Diabetes and Digestive and Kidney Diseases (R00DK088589, T32DK007202)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- gp130, YAP, notches, Src kinase, Yes, IL-6 family cytokines, intestinal epithelial regeneration, experimental colitis, epithelial cell proliferation, epithelial differentiation, barrier function
- MeSH terms
- YAP-Signaling Proteins, Animals, Body Weight, Cell Differentiation, Disease Models, Animal, Enzyme Activation, Epithelial Cells, Homeostasis, Humans, Inflammation, Intestinal Mucosa, Phosphoproteins, Regeneration, Inflammatory Bowel Diseases, Signal Transduction, Up-Regulation, Proto-Oncogene Proteins pp60(c-src), Cell Cycle Proteins, Adaptor Proteins, Signal Transducing, Cell Proliferation, Cytokine Receptor gp130, Mice, Proto-Oncogene Proteins c-yes, Receptors, Notch, HEK293 Cells
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