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DNMT3a-mediated methylation of TCF21/hnRNPA1 aggravates liver fibrosis by regulating the NF-κB signaling pathway

ABSTRACT: Hepatic fibrosis is caused by liver damage as a consequence of wound healing response. Recent studies have shown that hepatic fibrosis could be effectively reversed, partly through regression of activated hepatic stellate cells (HSCs). Transcription factor 21 (TCF21), a member of the basic helix-loop-helix (bHLH) transcription factor, is involved in epithelial-mesenchymal transformation in various diseases. However, the mechanism by which TCF21 regulates epithelial-mesenchymal transformation in hepatic fibrosis has not been elucidated. In this research, we found that hnRNPA1, the downstream binding protein of TCF21, accelerates liver fibrosis reversal by inhibiting the NF-κB signaling pathway. Furthermore, the combination of DNMT3a with TCF21 promoter results in TCF21 hypermethylation. Our results suggest that DNMT3a regulation of TCF21 is a significant event in reversing hepatic fibrosis. In conclusion, this research identifies a novel signaling axis, DNMT3a-TCF21-hnRNPA1, that regulates HSCs activation and liver fibrosis reversal, providing a novel treatment strategy for hepatic fibrosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE232674 | GEO | 2024/10/01

REPOSITORIES: GEO

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Expression data from HSCs

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2012-06-02 | E-GEOD-24588 | biostudies-arrayexpress

Expression data from HSCs

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Basic helix-loop-helix transcription factor Tcf21 is downstream target of male sex-determining gene SRY

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