Autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway.
Autophagy plays important roles in self-renewal and differentiation of stem cells. Hepatic progenitor cells (HPCs) are thought to have the ability of self-renewal as well as possess a bipotential capacity, which allows them to differentiate into both hepatocytes and bile ductular cells. However, how autophagy contributes to self-renewal and differentiation of hepatic progenitor cells is not well understood. In this study, we use a well-established rat hepatic progenitor cell lines called WB-F344, which is treated with 3.75 mM sodium butyrate (SB) to promote the differentiation of WB-F344 along the biliary phenotype. We found that autophagy was decreased in the early stage of biliary differentiation, and maintained a low level at the late stage. Activation of autophagy by rapamycin or starvation suppressed the biliary differentiation of WB-F344. Further study reported that autophagy inhibited Notch1 signaling pathway, which contributed to biliary differentiation and morphogenesis. In conclusions, autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway.
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.|c Fujian Medical University , Fuzhou , Fujian , China.
Jianxing
J
Zeng
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
Yingying
Y
Jing
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.|c Fujian Medical University , Fuzhou , Fujian , China.
Rongyu
R
Shi
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.|c Fujian Medical University , Fuzhou , Fujian , China.
Xiaorong
X
Pan
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.|c Fujian Medical University , Fuzhou , Fujian , China.
Fobao
F
Lai
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
Wenting
W
Liu
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
Rong
R
Li
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
Lu
L
Gao
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
Xiaojuan
X
Hou
b Department of Comprehensive Treatment , Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
Mengchao
M
Wu
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
Lixin
L
Wei
D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001652:Bile Ducts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020148:Butyric Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics / Q000378:metabolism; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000072100:Jagged-1 Protein / Q000235:genetics / Q000378:metabolism; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000072056:Transcription Factor HES-1 / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D020148:Butyric Acid; D051539:Hepatocyte Nuclear Factor 1-beta; D051559:Hepatocyte Nuclear Factor 6; D000072100:Jagged-1 Protein; D053539:Keratin-19; D051881:Receptor, Notch1; D012097:Repressor Proteins; D020123:Sirolimus; D000072056:Transcription Factor HES-1; C405694:Hairy, HRT1 protein; C489735:Hes1 protein, rat; C489686:Hes5 protein, rat; C068755:Hnf1b protein, rat; C000606275:Jag1 protein, rat; C497763:Notch1 protein, rat; C496607:Onecut1 protein, rat
Notch1; autophagy; biliary differentiation; hepatic progenitor cells