Nature Communications (Aug 2018)
The tyrosine phosphatase SHP2 controls TGFβ-induced STAT3 signaling to regulate fibroblast activation and fibrosis
- Ariella Zehender,
- Jingang Huang,
- Andrea-Hermina Györfi,
- Alexandru-Emil Matei,
- Thuong Trinh-Minh,
- Xiaohan Xu,
- Yi-Nan Li,
- Chih-Wei Chen,
- Jianping Lin,
- Clara Dees,
- Christian Beyer,
- Kolja Gelse,
- Zhong-Yin Zhang,
- Christina Bergmann,
- Andreas Ramming,
- Walter Birchmeier,
- Oliver Distler,
- Georg Schett,
- Jörg H. W. Distler
Affiliations
- Ariella Zehender
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Jingang Huang
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Andrea-Hermina Györfi
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Alexandru-Emil Matei
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Thuong Trinh-Minh
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Xiaohan Xu
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Yi-Nan Li
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Chih-Wei Chen
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Jianping Lin
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University
- Clara Dees
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Christian Beyer
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Kolja Gelse
- Department of Trauma Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU)
- Zhong-Yin Zhang
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University
- Christina Bergmann
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Andreas Ramming
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Walter Birchmeier
- Max Delbrück Center for Molecular Medicine (MDC)
- Oliver Distler
- Department of Rheumatology, University Hospital Zurich
- Georg Schett
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- Jörg H. W. Distler
- Department of Internal Medicine 3–Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen
- DOI
- https://doi.org/10.1038/s41467-018-05768-3
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 17
Abstract
Hyperactivation of TGFβ signaling is a common feature of fibrotic diseases. Here the authors show that genetic or pharmacologic inactivation of the tyrosine phosphatase SHP2 prevents TGFβ-induced JAK2/STAT3 signaling, inhibits fibroblast activation and exerts potent anti-fibrotic effects.