PMID- 37073611
OWN - NLM
STAT- MEDLINE
DCOM- 20230420
LR  - 20230519
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 37
IP  - 5
DP  - 2023 May
TI  - Yes-associated protein promotes the proliferation and differentiation of liver 
      progenitor cells during liver fibrosis.
PG  - e22916
LID - 10.1096/fj.202201919R [doi]
AB  - Liver fibrosis is closely related to the proliferation and differentiation of 
      liver progenitor cells (LPCs). Yes-associated protein (YAP) is a key effector 
      molecule of the Hippo signaling pathway and plays an important role in regulating 
      cell proliferation and liver homeostasis. However, its role in LPCs proliferation 
      and differentiation during liver fibrosis are not well understood. Using 
      immunohistochemistry, immunofluorescence staining, quantitative PCR and Western 
      blotting, we discovered that LPCs expansion and enhanced YAP expression in LPCs 
      in either choline-deficient, ethionine-supplemented (CDE) diet or 
      3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced fibrotic mice, as 
      well as in patients with liver fibrosis. By injecting adeno-associated virus 
      vectors under the transcriptional control of Lgr5 promoter, we found that 
      targeted knockdown of YAP in LPCs attenuated the CDE/DDC diet-induced ductular 
      reaction and liver fibrosis. Using EdU incorporation and Cell Counting Kit-8 
      assays, we demonstrated that YAP can modulate LPCs proliferation. Importantly, 
      spleen transplantation of YAP-overexpressing LPCs improved their ability to 
      differentiate into hepatocytes and alleviated carbon tetrachloride-induced liver 
      fibrosis. Collectively, our findings indicate that LPCs expansion and 
      differentiation during liver fibrosis could be modulated by YAP, further 
      suggesting the possibility of manipulating YAP expression in LPCs as a potential 
      treatment for chronic liver diseases.
CI  - (c) 2023 Federation of American Societies for Experimental Biology.
FAU - Shen, Zhenyang
AU  - Shen Z
AD  - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
AD  - Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Dai, Weiming
AU  - Dai W
AD  - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
AD  - Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Guo, Yuecheng
AU  - Guo Y
AD  - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
AD  - Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Wang, Junjun
AU  - Wang J
AD  - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
AD  - Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Shen, Bo
AU  - Shen B
AD  - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
AD  - Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Li, Binghang
AU  - Li B
AD  - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
AD  - Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Lu, Lungen
AU  - Lu L
AD  - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
AD  - Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Cai, Xiaobo
AU  - Cai X
AUID- ORCID: 0000-0001-7697-5873
AD  - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
AD  - Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (YAP-Signaling Proteins)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *YAP-Signaling Proteins
MH  - *Liver Cirrhosis/metabolism
MH  - Liver/metabolism
MH  - Hepatocytes/pathology
MH  - Stem Cells/pathology
MH  - Cell Differentiation
MH  - Cell Proliferation
OTO - NOTNLM
OT  - Yes-associated protein
OT  - ductular reaction
OT  - liver fibrosis
OT  - liver progenitor cells
OT  - transplantation
EDAT- 2023/04/19 06:41
MHDA- 2023/04/20 06:42
CRDT- 2023/04/19 04:02
PHST- 2023/02/27 00:00 [revised]
PHST- 2022/11/17 00:00 [received]
PHST- 2023/03/29 00:00 [accepted]
PHST- 2023/04/20 06:42 [medline]
PHST- 2023/04/19 06:41 [pubmed]
PHST- 2023/04/19 04:02 [entrez]
AID - 10.1096/fj.202201919R [doi]
PST - ppublish
SO  - FASEB J. 2023 May;37(5):e22916. doi: 10.1096/fj.202201919R.