AI Article Synopsis
- HMGB1 is crucial for causing liver injury and fibrosis, promoting the activation and growth of hepatic stellate cells (HSCs) and increasing collagen and α-SMA protein levels.
- The increase in HSC proliferation due to HMGB1 is linked to the upregulation of miR-146b, which negatively regulates HNF1A expression.
- Targeting and inhibiting HMGB1 can alleviate liver fibrosis, indicating that the HMGB1/p65/miR-146b/HNF1A signaling pathway plays a significant role in liver fibrogenesis.
Article Abstract
High mobility group box 1 (HMGB1) is essential for the pathogenesis of liver injury and liver fibrosis. We previously revealed that miR-146b promotes hepatic stellate cells (HSCs) activation and proliferation. Nevertheless, the potential mechanisms are still unknown. Herein, HMGB1 increased HSCs proliferation and COL1A1 and α-SMA protein levels. However, the knockdown of miR-146b inhibited HSCs proliferation and COL1A1 and α-SMA protein levels induced via HMGB1 treatment. miR-146b was upregulated by HMGB1 and miR-146b targeted hepatocyte nuclear factor 1A (HNF1A) 3untranslated region (3UTR) to modulate its expression negatively. Further, we confirmed that HMGB1 might elicit miR-146b expression via p65 within HSCs. Knockdown or block of HMGB1 relieved the CCl-induced liver fibrosis. In fibrotic liver tissues, miR-146b expression was positively correlated with p65 mRNA, but HNF1A mRNA was inversely correlated with p65, and miR-146b expression. In summary, our findings suggest that HMGB1/p65/miR-146b/HNF1A signaling exerts a crucial effect on liver fibrogenesis via the regulation of HSC function.
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| http://dx.doi.org/10.1089/dna.2019.5330 | DOI Listing |
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