Liver progenitor cells (LPCs) have a remarkable contribution to the hepatocytes and ductal cells when normal hepatocyte proliferation is severely impaired. As a biomarker for LPCs, Sry-box 9 (Sox9) plays critical roles in liver homeostasis and repair in response to injury. However, the regulation mechanism of Sox9 in liver physiological and pathological state remains unknown. In this study, we found that miR-126 positively regulated the expression of Sox9, the proliferation and differentiation of SOX9⁺ LPCs by suppressing the translation of homeobox b6 (Hoxb6). As a transcription factor, HOXB6 directly binds to the promoter of Sox9 to inhibit Sox9 expression, resulting in the destruction of the properties of SOX9⁺ LPCs in CCl₄-induced liver injury. These findings revealed the role of miR-126 in regulating SOX9⁺ LPCs fate by targeting Hoxb6 in liver injury repair. Our findings suggest the potential role of miR-126 as a nucleic acid therapy drug target for liver failure.

当正常肝细胞增殖受到严重损害时，肝祖细胞（LPC）对肝细胞和导管细胞有显着贡献。作为LPC的生物标志物，Sry-box 9（Sox9）在肝脏动态平衡和响应损伤的修复中起着关键作用。然而，Sox9在肝脏生理和病理状态中的调节机制仍然未知。在这项研究中，我们发现miR-126通过抑制同源异型盒b6（Hoxb6）的翻译正调控Sox9的表达，SOX9 ⁺ LPC的增殖和分化。作为转录因子，HOXB6直接与Sox9的启动子结合抑制Sox9表达，导致破坏CCl ₄所致肝损伤中SOX9 ⁺ LPCs的特性。这些发现揭示了miR-126通过靶向Hoxb6在肝损伤修复中调节SOX9 ⁺ LPC命运的作用。我们的发现表明，miR-126作为肝衰竭的核酸治疗药物靶标的潜在作用。