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Status: Bibliographieeintrag

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Verfasst von:Li, Ting [VerfasserIn]   i
 Eheim, Ashley [VerfasserIn]   i
 Klein, Sabine [VerfasserIn]   i
 Uschner, Frank E. [VerfasserIn]   i
 Smith, Amber C. [VerfasserIn]   i
 Brandon‐Warner, Elizabeth [VerfasserIn]   i
 Ghosh, Sriparna [VerfasserIn]   i
 Bonkovsky, Herbert L. [VerfasserIn]   i
 Trebicka, Jonel [VerfasserIn]   i
 Schrum, Laura W. [VerfasserIn]   i
Titel:Novel role of nuclear receptor rev-erbα in hepatic stellate cell activation
Titelzusatz:potential therapeutic target for liver injury
Verf.angabe:Ting Li, Ashley L. Eheim, Sabine Klein, Frank E. Uschner, Amber C. Smith, Elizabeth Brandon‐Warner, Sriparna Ghosh, Herbert L. Bonkovsky, Jonel Trebicka, and Laura W. Schrum
E-Jahr:2014
Jahr:4 February 2014
Umfang:14 S.
Fussnoten:Gesehen am 17.08.2020
Titel Quelle:Enthalten in: Hepatology
Ort Quelle:New York [u.a.] : Wiley Interscience, 1981
Jahr Quelle:2014
Band/Heft Quelle:59(2014), 6, Seite 2383-2396
ISSN Quelle:1527-3350
Abstract:Hepatic stellate cell (HSC) transdifferentiation from a quiescent, adipocyte-like cell to a highly secretory and contractile myofibroblast-like phenotype contributes to negative pathological consequences, including fibrosis/cirrhosis with portal hypertension (PH). Antiadipogenic mechanisms have been shown to underlie activation of HSCs. We examined the role of heme-sensing nuclear receptor Rev-erbα, a transcriptional repressor involved in metabolic and circadian regulation known to promote adipogenesis in preadipocytes, in HSC transdifferentiation. We discovered that Rev-erbα protein was up-regulated in activated HSCs and injured livers; however, transcriptional repressor activity was not affected by fibrogenic treatments. Surprisingly, increased protein expression was accompanied with increased cytoplasmic accumulation of Rev-erbα, which demonstrated distributions similar to myosin, the major cellular motor protein. Cells overexpressing a cytoplasm-localized Rev-erbα exhibited enhanced contractility. Ectopically expressed Rev-erbα responded to both adipogenic ligand and fibrogenic transforming growth factor beta treatment. Rev-erb ligand SR6452 down-regulated cytoplasmic expression of Rev-erbα, decreased expression of fibrogenic markers and the activated phenotype in HSCs, and ameliorated fibrosis and PH in rodent models. Conclusions: Up-regulation of Rev-erbα is an intrinsic fibrogenic response characterized by cytoplasmic accumulation of the protein in activated HSCs. Cytoplasmic expression of Rev-erbα promotes a contractile phenotype. Rev-erbα acts as a bifunctional regulator promoting either anti- or profibrogenic response, depending on milieu. Rev-erb ligand SR6452 functions by a previously undescribed mechanism, targeting both nuclear activity and cytoplasmic expression of Rev-erbα. Our studies identify Rev-erbα as a novel regulator of HSC transdifferentiation and offers exciting new insights on the therapeutic potential of Rev-erb ligands. (Hepatology 2014;59:2383-2396)
DOI:doi:10.1002/hep.27049
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1002/hep.27049
 Volltext: https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.27049
 DOI: https://doi.org/10.1002/hep.27049
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1727143744
Verknüpfungen:→ Zeitschrift

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