| Online-Ressource |
Verfasst von: | Li, Ting [VerfasserIn]  |
| Eheim, Ashley [VerfasserIn]  |
| Klein, Sabine [VerfasserIn]  |
| Uschner, Frank E. [VerfasserIn]  |
| Smith, Amber C. [VerfasserIn]  |
| Brandon‐Warner, Elizabeth [VerfasserIn]  |
| Ghosh, Sriparna [VerfasserIn]  |
| Bonkovsky, Herbert L. [VerfasserIn]  |
| Trebicka, Jonel [VerfasserIn]  |
| Schrum, Laura W. [VerfasserIn]  |
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 |
Novel role of nuclear receptor rev-erbα in hepatic stellate cell activation / Li, Ting [VerfasserIn]; 4 February 2014 (Online-Ressource)