Nrf2 protects stellate cells from Smad-dependent cell activation
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Autor:innen
Prestigiacomo, Vincenzo
Autor:in (Körperschaft)
Publikationsdatum
07/2018
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
PLOS ONE
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
13
Ausgabe / Nummer
7
Seiten / Dauer
Patentnummer
Verlag / Herausgebende Institution
Public Library of Science
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Hepatic stellate cells (HSC) orchestrate the deposition of extracellular matrix (ECM) and are the primary effector of liver fibrosis. Several factors, including TGF-β1, PDGF and oxidative stress, have been shown to trigger HSC activation. However, the involvement of cellular defence mechanisms, such as the activation of antioxidant response by Nrf2/Keap1 in the modulation of HSC activation is not known. The aim of this work was to elucidate the role of Nrf2 pathway in HSC trans-differentiation involved in the development of fibrosis. To this end, we repressed Nrf2 and Keap1 expression in HSC with specific siRNAs. We then assessed activation markers, as well as proliferation and migration, in both primary and immortalised human HSCs exposed to Smad inhibitors (SB-431542 hydrate and SB-525334), TGF-β1 and/or PDGF. Our results indicate that knocking down Nrf2 induces HSC activation, as shown by an increase in αSMA-positive cells and by gene expression induction of ECM components (collagens and fibronectin). HSC with reduced Nrf2-levels also showed an increase in migration and a decrease in proliferation. We could also demonstrate that the activation of Nrf2-deficient HSC involves the TGF-β1/Smad pathway, as the activation was successfully inhibited with the two tested Smad inhibitors. Moreover, TGF-β1 elicited a stronger induction of HSC activation markers in Nrf2 deficient cells than in wild type cells. Thus, our data suggest that Nrf2 limits HSCs activation, through the inhibition of the TGF-β1/Smad pathway in HSCs.
Schlagwörter
TGF-β1, Nrf2, Hepatic stellate cells (HSC), extracellular matrix (ECM), Liver fibrosis
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1932-6203
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
Prestigiacomo, V., & Suter-Dick, L. (2018). Nrf2 protects stellate cells from Smad-dependent cell activation. Plos One, 13(7). https://doi.org/10.1371/journal.pone.0201044