Tribbles homologue 3 stimulates canonical TGF-beta signalling to regulate fibroblast activation and tissue fibrosis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F16%3A10325226" target="_blank" >RIV/00216208:11110/16:10325226 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1136/annrheumdis-2014-206234" target="_blank" >http://dx.doi.org/10.1136/annrheumdis-2014-206234</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1136/annrheumdis-2014-206234" target="_blank" >10.1136/annrheumdis-2014-206234</a>

Result language

angličtina

Original language name

Tribbles homologue 3 stimulates canonical TGF-beta signalling to regulate fibroblast activation and tissue fibrosis

Original language description

Objectives Tribbles homologue 3 (TRB3) is a pseudokinase that modifies the activation of various intracellular signalling pathways to control fundamental processes extending from mitosis and cell activation to apoptosis and modulation of gene expression. Here, we aimed to analyse the role of TRB3 in fibroblast activation in systemic sclerosis (SSc). Methods The expression of TRB3 was quantified by quantitative PCR, western blot and immunohistochemistry. The role of TRB3 was analysed in cultured fibroblasts and in experimental fibrosis using small interfering RNA (siRNA)-mediated knockdown and overexpression of TRB3. Results TRB3 expression was increased in fibroblasts of patients with SSc and in murine models of SSc in a transforming growth factor-beta (TGF-beta)/Smad-dependent manner. Overexpression of TRB3 stimulated canonical TGF-beta signalling and induced an activated phenotype in resting fibroblasts. In contrast, knockdown of TRB3 reduced the profibrotic effects of TGF-beta and decreased the collagen synthesis. Moreover, siRNA-mediated knockdown of TRB3 exerted potent antifibrotic effects and ameliorated bleomycin as well as constitutively active TGF-beta receptor I-induced fibrosis with reduced dermal thickening, decreased hydroxyproline content and impaired myofibroblast differentiation. Conclusions The present study characterises TRB3 as a novel profibrotic mediator in SSc. TGF-beta induces TRB3, which in turn activates canonical TGF-beta/Smad signalling and stimulates the release of collagen, thereby inducing a positive feedback loop that may contribute to aberrant TGF-beta signalling in SSc.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FE - Other fields of internal medicine

OECD FORD branch

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Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2016

Confidentiality

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

Name of the periodical

Annals of the Rheumatic Diseases

ISSN

0003-4967

e-ISSN

—

Volume of the periodical

75

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

609-616

UT code for WoS article

000371077700020

EID of the result in the Scopus database

2-s2.0-84960115459