Orphan nuclear receptor NR4A1 regulates transforming growth factor-beta signaling and fibrosis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F15%3A10294722" target="_blank" >RIV/00216208:11110/15:10294722 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023728:_____/15:#0005052

Výsledek na webu

<a href="http://dx.doi.org/10.1038/nm.3777" target="_blank" >http://dx.doi.org/10.1038/nm.3777</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/nm.3777" target="_blank" >10.1038/nm.3777</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Orphan nuclear receptor NR4A1 regulates transforming growth factor-beta signaling and fibrosis

Popis výsledku v původním jazyce

Mesenchymal responses are an essential aspect of tissue repair. Failure to terminate this repair process correctly, however, results in fibrosis and organ dysfunction. Therapies that block fibrosis and restore tissue homeostasis are not yet available forclinical use. Here we characterize the nuclear receptor NR4A1 as an endogenous inhibitor of transforming growth factor-beta (TGF-beta) signaling and as a potential target for anti-fibrotic therapies. NR4A1 recruits a repressor complex comprising SP1, SIN3A, CoREST, LSD1, and HDAC1 to TGF-beta target genes, thereby limiting pro-fibrotic TGF-beta effects. Even though temporary upregulation of TGF-beta in physiologic wound healing induces NR4A1 expression and thereby creates a negative feedback loop, thepersistent activation of TGF-beta signaling in fibrotic diseases uses AKT- and HDAC-dependent mechanisms to inhibit NR4A1 expression and activation. Small-molecule NR4A1 agonists can overcome this lack of active NR4A1 and inhibit experime

Název v anglickém jazyce

Orphan nuclear receptor NR4A1 regulates transforming growth factor-beta signaling and fibrosis

Popis výsledku anglicky

Mesenchymal responses are an essential aspect of tissue repair. Failure to terminate this repair process correctly, however, results in fibrosis and organ dysfunction. Therapies that block fibrosis and restore tissue homeostasis are not yet available forclinical use. Here we characterize the nuclear receptor NR4A1 as an endogenous inhibitor of transforming growth factor-beta (TGF-beta) signaling and as a potential target for anti-fibrotic therapies. NR4A1 recruits a repressor complex comprising SP1, SIN3A, CoREST, LSD1, and HDAC1 to TGF-beta target genes, thereby limiting pro-fibrotic TGF-beta effects. Even though temporary upregulation of TGF-beta in physiologic wound healing induces NR4A1 expression and thereby creates a negative feedback loop, thepersistent activation of TGF-beta signaling in fibrotic diseases uses AKT- and HDAC-dependent mechanisms to inhibit NR4A1 expression and activation. Small-molecule NR4A1 agonists can overcome this lack of active NR4A1 and inhibit experime

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FE - Ostatní obory vnitřního lékařství

OECD FORD obor

—

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Nature Medicine

ISSN

1078-8956

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

150-158

Kód UT WoS článku

000348974800017

EID výsledku v databázi Scopus

2-s2.0-84925537240