Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis

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Details zur Publikation

Autorinnen und Autoren: Chakraborty D, Sumova B, Mallano T, Chen CW, Distler A, Bergmann C, Ludolph I, Horch RE, Gelse K, Ramming A, Distler O, Schett G, Senolt L, Distler J
Zeitschrift: Nature Communications
Jahr der Veröffentlichung: 2017
Band: 8
Heftnummer: 1
Seitenbereich: 1130
ISSN: 2041-1723


Abstract


Signal transducer and activator of transcription 3 (STAT3) is phosphorylated by various kinases, several of which have been implicated in aberrant fibroblast activation in fibrotic diseases including systemic sclerosis (SSc). Here we show that profibrotic signals converge on STAT3 and that STAT3 may be an important molecular checkpoint for tissue fibrosis. STAT3 signaling is hyperactivated in SSc in a TGF?-dependent manner. Expression profiling and functional studies in vitro and in vivo demonstrate that STAT3 activation is mediated by the combined action of JAK, SRC, c-ABL, and JNK kinases. STAT3-deficient fibroblasts are less sensitive to the pro-fibrotic effects of TGF?. Fibroblast-specific knockout of STAT3, or its pharmacological inhibition, ameliorate skin fibrosis in experimental mouse models. STAT3 thus integrates several profibrotic signals and might be a core mediator of fibrosis. Considering that several STAT3 inhibitors are currently tested in clinical trials, STAT3 might be a candidate for molecular targeted therapies of SSc.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Distler, Jörg PD Dr.
Heisenberg-Professur für Molekulare Mechanismen der Organfibrose
Horch, Raymund E. Prof. Dr.
Professur für Plastische Chirurgie und Handchirurgie
Mallano, Tatjana
Medizinische Klinik 3 - Rheumatologie und Immunologie
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III


Einrichtungen weiterer Autorinnen und Autoren

Universitätsspital Zürich (USZ)
Univerzita Karlova v Praze / Charles University in Prague


Zitierweisen

APA:
Chakraborty, D., Sumova, B., Mallano, T., Chen, C.-W., Distler, A., Bergmann, C.,... Distler, J. (2017). Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis. Nature Communications, 8(1), 1130. https://dx.doi.org/10.1038/s41467-017-01236-6

MLA:
Chakraborty, Debomita, et al. "Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis." Nature Communications 8.1 (2017): 1130.

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