Department of Gastroenterology, Shanghai Tenth People's Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China.
J Cell Mol Med. 2020 Dec;24(23):14050-14058. doi: 10.1111/jcmm.16017. Epub 2020 Oct 30.
Recently, the incidence of bile duct-related diseases continues to increase, and there is no effective drug treatment except liver transplantation. However, due to the limited liver source and expensive donations, clinical application is often limited. Although current studies have shown that ductular reaction cells (DRCs) reside in the vicinity of peribiliary glands can differentiate into cholangiocytes and would be an effective alternative to liver transplantation, the role and mechanism of DRCs in cholangiole physiology and bile duct injury remain unclear. A 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-enriched diet was used to stimulate DRCs proliferation. Our research suggests DRCs are a type of intermediate stem cells with proliferative potential that exist in the bile duct injury. Meanwhile, DRCs have bidirectional differentiation potential, which can differentiate into hepatocytes and cholangiocytes. Furthermore, we found DRCs highly express Lgr5, and Lgr5 is a molecular marker for neonatal DRCs (P < .05). Finally, we confirmed Wnt/β-catenin signalling achieves bile duct regeneration by regulating the expression of Lgr5 genes in DRCs (P < .05). We described the regenerative potential of DRCs and reveal opportunities and source for the treatment of cholestatic liver diseases.
最近，胆管相关疾病的发病率不断上升，除肝移植外，尚无有效的药物治疗方法。然而，由于肝脏来源有限且捐赠昂贵，临床应用往往受到限制。尽管目前的研究表明，胆管周围腺附近存在胆管反应细胞（DRC），可分化为胆管细胞，将成为肝移植的有效替代方法，但 DRC 在胆管生理和胆管损伤中的作用和机制仍不清楚。我们使用富含 3,5-二乙氧羰基-1,4-二氢吡啶（DDC）的饮食来刺激 DRC 增殖。我们的研究表明，DRC 是一种具有增殖潜能的中间干细胞，存在于胆管损伤中。同时，DRC 具有双向分化潜能，可分化为肝细胞和胆管细胞。此外，我们发现 DRCs 高表达 Lgr5，而 Lgr5 是新生儿 DRCs 的分子标志物（P<.05）。最后，我们证实 Wnt/β-catenin 信号通过调节 DRCs 中 Lgr5 基因的表达来实现胆管再生（P<.05）。我们描述了 DRC 的再生潜能，并揭示了治疗胆汁淤积性肝病的机会和来源。
