Wnt/β-catenin signalling controls bile duct regeneration by regulating differentiation of ductular reaction cells.
Nan WangRui KongWei HanJie LuPublished in: Journal of cellular and molecular medicine (2020)
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.
Keyphrases
- stem cells
- induced apoptosis
- cell proliferation
- cell cycle arrest
- epithelial mesenchymal transition
- liver injury
- signaling pathway
- poor prognosis
- drug induced
- mesenchymal stem cells
- risk factors
- endoplasmic reticulum stress
- oxidative stress
- gene expression
- bone marrow
- replacement therapy
- genome wide identification
- pi k akt
- long non coding rna
- transcription factor
- adverse drug
- single cell
- liver fibrosis
- electron transfer
- smoking cessation
- genome wide analysis