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) 3′-untranslated region (3′UTR) 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 CCl₄-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.

中文翻译：

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HMGB1通过p65 / miR-146b信号传导抑制HNF1A调节肝纤维化。

高迁移率族1盒（HMGB1）对于肝损伤和肝纤维化的发病机制至关重要。我们先前发现，miR-146b促进肝星状细胞（HSC）的激活和增殖。然而，潜在的机制仍然未知。在本文中，HMGB1增加了HSC的增殖以及COL1A1和α-SMA蛋白的水平。但是，敲低miR-146b会抑制HMGB1处理诱导的HSC增殖以及COL1A1和α-SMA蛋白水平。的miR-146B是由HMGB1和miR-146b中靶向肝细胞核因子1A（HNF1A）3上调' -非翻译区（3 ' UTR）来负调节其表达。此外，我们证实HMGB1可能通过HSC中的p65引起miR-146b表达。击倒或阻止HMGB1释放了CCl ₄引起的肝纤维化。在肝纤维化组织中，miR-146b表达与p65 mRNA呈正相关，而HNF1A mRNA与p65和miR-146b表达呈负相关。总而言之，我们的发现表明HMGB1 / p65 / miR-146b / HNF1A信号传导通过调节HSC功能对肝纤维化发挥关键作用。