In:
The FEBS Journal, Wiley, Vol. 281, No. 1 ( 2014-01), p. 88-103
Abstract:
Phosphatase and tensin homologue deleted on chromosome 10 ( PTEN ) has been reported to play a role in the suppression of activated hepatic stellate cells ( HSC s). Moreover, it has been demonstrated that hypermethylation of the PTEN promoter is responsible for the loss of PTEN expression during HSC activation. Methylation is now established as a fundamental regulator of gene transcription. Micro RNA s (mi RNA s), which can control gene expression by binding to their target genes for degradation and/or translational repression, were found to be involved in liver fibrosis. However, the mechanism responsible for mi RNA ‐mediated epigenetic regulation in liver fibrosis still remained unclear. In the present study, curcumin treatment significantly resulted in the inhibition of cell proliferation and an increase in the apoptosis rate through the up‐regulation of PTEN associated with a decreased DNA methylation level. Only DNA methyltransferase 3b ( DNMT 3b) was reduced in vivo and in vitro after curcumin treatment. Further studies were performed aiming to confirm that the knockdown of DNMT 3b enhanced the loss of PTEN methylation by curcumin. In addition, miR‐29b was involved in the hypomethylation of PTEN by curcumin. MiR‐29b not only was increased by curcumin in activated HSC s, but also was confirmed to target DNMT 3b by luciferase activity assays. Curcumin‐mediated PTEN up‐regulation, DNMT 3b down‐regulation and PTEN hypomethylation were all attenuated by miR‐29b inhibitor. Collectively, it is demonstrated that curcumin can up‐regulate miR‐29b expression, resulting in DNMT 3b down‐regulation in HSC s and epigenetically‐regulated PTEN involved in the suppression of activated HSC s. These results indicate that mi RNA ‐mediated epigenetic regulation may be a novel mechanism suppressing liver fibrosis.
Type of Medium:
Online Resource
ISSN:
1742-464X
,
1742-4658
DOI:
10.1111/febs.2013.281.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2172518-4
SSG:
12
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