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Compound
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Target Concepts:
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Query: UMLS:C0239946 (
liver fibrosis
)
8,268
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Activation of hepatic stellate cells (HSC) is a hallmark event in
liver fibrosis
. Accumulation of reactive oxygen species (ROS) serves as a driving force for HSC activation. The regulatory subunits of the NOX complex, NCF1 (p47
phox
) and
NCF2
(p67
phox
), are up-regulated during HSC activation contributing to ROS production and
liver fibrosis
. The transcriptional mechanism underlying NCF1/2 up-regulation is not clear. In the present study we investigated the role of serum response factor (SRF) in HSC activation focusing on the transcriptional regulation of NCF1/2. We report that compared to wild type littermates HSC-conditional SRF knockout (CKO) mice exhibited a mortified phenotype of
liver fibrosis
induced by thioacetamide (TAA) injection or feeding with a methionine-and-choline deficient diet (MCD). More importantly, SRF deletion attenuated ROS levels in HSCs in vivo. Similarly, SRF knockdown in cultured HSCs suppressed ROS production in vitro. Further analysis revealed that SRF deficiency resulted in repression of NCF1/
NCF2
expression. Mechanistically, SRF regulated epigenetic transcriptional activation of NCF1/
NCF2
by interacting with and recruiting the histone acetyltransferase KAT8 during HSC activation. In conclusion, we propose that SRF integrates transcriptional activation of NCF1/
NCF2
and ROS production to promote
liver fibrosis
.
...
PMID:Serum response factor (SRF) promotes ROS generation and hepatic stellate cell activation by epigenetically stimulating NCF1/2 transcription. 3144 11
