Abramczyk Joanna, Milkiewicz Malgorzata, Łaba Alicja, Milkiewicz Piotr, Banales Jesus M, Kempinska-Podhorodecka Agnieszka
Department of Medical Biology, Pomeranian Medical University, 70-111 Szczecin, Poland.
Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland.
Int J Mol Sci. 2025 Aug 12;26(16):7784. doi: 10.3390/ijms26167784.
Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with male predominance. This study investigated the role of microRNA-125b in PSC-related liver fibrosis, focusing on its interaction with transforming growth factor beta (TGF-β), androgen receptors (ARs), and apelin. Elevated serum and hepatic levels of miR-125b were observed in PSC patients, particularly in males and those with advanced fibrosis, and correlated with increased liver injury markers and FibroScan stiffness. miR-125b expression negatively correlated with apelin and TGF-β levels, while it positively correlated with AR expression. In vitro, miR-125b overexpression induced ARs and suppressed p53 and apelin, whereas lipopolysaccharide stimulation reduced miR-125b and enhanced pro-inflammatory genes, including TNF-α and TGF-β. Notably, ursodeoxycholic acid therapy significantly decreased serum miR-125b levels. These findings suggest that miR-125b contributes to inflammation and fibrogenesis in PSC, partly through the modulation of TGF-β, ARs, and apelin signalling. Moreover, the observed sex-based differences in miR-125b expression underscore the influence of androgens in PSC pathogenesis.
原发性硬化性胆管炎（PSC）是一种以男性为主的胆汁淤积性肝病。本研究调查了微小RNA-125b在PSC相关肝纤维化中的作用，重点关注其与转化生长因子β（TGF-β）、雄激素受体（ARs）和apelin的相互作用。在PSC患者中观察到血清和肝脏中miR-125b水平升高，尤其是男性患者和肝纤维化晚期患者，且与肝损伤标志物升高和FibroScan硬度相关。miR-125b表达与apelin和TGF-β水平呈负相关，而与AR表达呈正相关。在体外，miR-125b过表达诱导ARs表达并抑制p53和apelin，而脂多糖刺激降低miR-125b水平并增强包括TNF-α和TGF-β在内的促炎基因表达。值得注意的是，熊去氧胆酸治疗可显著降低血清miR-125b水平。这些发现表明，miR-125b在PSC的炎症和纤维化形成中起作用，部分是通过调节TGF-β、ARs和apelin信号通路。此外，观察到的miR-125b表达的性别差异强调了雄激素在PSC发病机制中的影响。
