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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10364912" target="_blank" >RIV/00216208:11110/17:10364912 - isvavai.cz</a>

Alternative codes found

RIV/00023728:_____/17:N0000011

Result on the web

<a href="http://dx.doi.org/10.1038/s41467-017-01236-6" target="_blank" >http://dx.doi.org/10.1038/s41467-017-01236-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-017-01236-6" target="_blank" >10.1038/s41467-017-01236-6</a>

Result language

angličtina

Original language name

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

Original language description

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 beta-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 beta. 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30226 - Rheumatology

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications [online]

ISSN

2041-1723

e-ISSN

—

Volume of the periodical

8

Issue of the periodical within the volume

October

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

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UT code for WoS article

000413573000025

EID of the result in the Scopus database

2-s2.0-85032222646