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dc.contributor.authorPrestigiacomo, Vincenzo
dc.contributor.authorSuter-Dick, Laura
dc.date.accessioned2018-12-14T15:42:11Z
dc.date.available2018-12-14T15:42:11Z
dc.date.issued2018-07
dc.identifier.doi10.1371/journal.pone.0201044. eCollection 2018.
dc.identifier.urihttp://hdl.handle.net/11654/26979
dc.description.abstractHepatic 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.
dc.description.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054401/
dc.language.isoen
dc.relation.ispartofPLoS ONE
dc.accessRightsAnonymous
dc.subjectTGF-β1
dc.subjectNrf2
dc.subjectHepatic stellate cells (HSC)
dc.subjectextracellular matrix (ECM)
dc.subjectLiver fibrosis
dc.titleNrf2 protects stellate cells from Smad-dependent cell activation.
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume13
dc.issue7
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandNo
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


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