Notch signaling pathway participates in the differentiation of hepatic progenitor cells into bile duct epithelial cells and progression of hepatic fibrosis in cholestatic liver fibrosis rat
10.3760/cma.j.issn.0529-5807.2017.06.007
- VernacularTitle: Notch信号通路参与大鼠胆汁性肝纤维化肝祖细胞向胆管上皮细胞分化以及肝纤维化进展
- Author:
Yongping MU
1
,
2
;
Xiao ZHANG
;
Ying XU
;
Weiwei FAN
;
Xuewei LI
;
Jiamei CHEN
;
Gaofeng CHEN
;
Ping LIU
Author Information
1. Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
2. Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Publication Type:Journal Article
- Keywords:
Cholestasis;
Notch signaling pathway;
Liver cirrhosis
- From:
Chinese Journal of Pathology
2017;46(6):400-405
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate differentiation direction of hepatic progenitor cells (HPCs) in cholestatic liver fibrosis (CLF), and the role of Notch signaling pathway in the differentiation of HPCs.
Methods:A CLF rat model was established by bile duct ligation (BDL) followed by monitoring changes of Notch signal pathway and the cellular origin of proliferating cholangiocytes. After intraperitoneal injection of DAPT (a Notch signaling inhibitor) after bile duct ligation, the progress of liver fibrosis and the proliferation of cholangiocytes after inhibition of the Notch pathway were analyzed.
Results:Data showed that bile duct proliferation gradually increased along with inflammatory cell infiltration and proliferating bile duct cells surrounded by abundant collagen in the BDL group. Immunostaining confirmed markedly increased expression of CK19, OV6, Sox9 and EpCAM. In addition, RT-PCR results showed that Notch signaling pathway was activated significantly. Once the Notch signaling pathway was inhibited by DAPT, bile duct proliferation markedly suppressed along with significantly decreased the mRNA expression of CK19, OV6, Sox9 and EpCAM, compared with BDL group [(10.2±0.7) vs. (22.3±0.8), (7.6±1.5) vs. (18.1±3.7), (1.4±0.4) vs. (4.1±1.1), (1.3±0.3) vs. (5.0±1.4), respectively, P<0.01]. Moreover, liver fibrosis was also reduced significantly.
Conclusion:Notch signaling activation is required for HPCs differentiation into cholangiocytes in CLF and inhibition of the Notch signaling pathway may offer a therapeutic option for treating CLF.
