PMID- 29907129
OWN - NLM
STAT- MEDLINE
DCOM- 20190312
LR  - 20190312
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Jun 15
TI  - A pivotal role of BEX1 in liver progenitor cell expansion in mice.
PG  - 164
LID - 10.1186/s13287-018-0905-2 [doi]
LID - 164
AB  - BACKGROUND: The activation and expansion of bipotent liver progenitor cells 
      (LPCs) are indispensable for liver regeneration after severe or chronic liver 
      injury. However, the underlying molecular mechanisms regulating LPCs and 
      LPC-mediated liver regeneration remain elusive. METHODS: Hepatic brain-expressed 
      X-linked 1 (BEX1) expression was evaluated using microarray screening, real-time 
      polymerase chain reaction, immunoblotting and immunofluorescence. LPC activation 
      and liver injury were studied following a choline-deficient, 
      ethionine-supplemented (CDE) diet in wild-type (WT) and Bex1(-/-) mice. 
      Proliferation, apoptosis, colony formation and hepatic differentiation were 
      examined in LPCs from WT and Bex1(-/-) mice. Peroxisome proliferator-activated 
      receptor gamma was detected in Bex1-deficient LPCs and mouse livers, and was 
      silenced to analyse the expansion of LPCs from WT and Bex1(-/-) mice. RESULTS: 
      Hepatic BEX1 expression was increased during CDE diet-induced liver injury and 
      was highly elevated primarily in LPCs. Bex1(-/-) mice fed a CDE diet displayed 
      impaired LPC expansion and liver regeneration. Bex1 deficiency inhibited LPC 
      proliferation and enhanced LPC apoptosis in vitro. Additionally, Bex1 deficiency 
      inhibited the colony formation of LPCs but had no effect on their hepatic 
      differentiation. Mechanistically, BEX1 inhibited peroxisome 
      proliferator-activated receptor gamma to promote LPC expansion. CONCLUSION: Our 
      findings indicate that BEX1 plays a pivotal role in LPC activation and expansion 
      during liver regeneration, potentially providing novel targets for liver 
      regeneration and chronic liver disease therapies.
FAU - Gu, Yuting
AU  - Gu Y
AD  - Pediatric Institute of Soochow University, Institutes for Translational Medicine, 
      Soochow University, Suzhou, Jiangsu, China.
AD  - Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Wei, Weiting
AU  - Wei W
AD  - Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 
      Yueyang Road, Shanghai, 200031, China.
FAU - Cheng, Yiji
AU  - Cheng Y
AD  - Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 
      Yueyang Road, Shanghai, 200031, China.
FAU - Wan, Bing
AU  - Wan B
AD  - Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 
      Yueyang Road, Shanghai, 200031, China.
FAU - Ding, Xinyuan
AU  - Ding X
AD  - Department of Pharmacy, the Affiliated Suzhou Municipal Hospital, Nanjing Medical 
      University, Suzhou, Jiangsu, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 
      Yueyang Road, Shanghai, 200031, China.
FAU - Zhang, Yanyun
AU  - Zhang Y
AUID- ORCID: 0000-0002-8990-8220
AD  - Pediatric Institute of Soochow University, Institutes for Translational Medicine, 
      Soochow University, Suzhou, Jiangsu, China. yyzhang@sibs.ac.cn.
AD  - Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 
      Yueyang Road, Shanghai, 200031, China. yyzhang@sibs.ac.cn.
FAU - Jin, Min
AU  - Jin M
AD  - Pediatric Institute of Soochow University, Institutes for Translational Medicine, 
      Soochow University, Suzhou, Jiangsu, China. mjin@sibs.ac.cn.
AD  - Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 
      Yueyang Road, Shanghai, 200031, China. mjin@sibs.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180615
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (BEX1 protein, human)
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
MH  - Animals
MH  - Liver/*pathology
MH  - Liver Regeneration/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/*genetics
PMC - PMC6002993
OTO - NOTNLM
OT  - Brain expressed X-linked 1
OT  - Expansion
OT  - Liver progenitor cells
OT  - Peroxisome proliferator-activated receptor gamma
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All procedures were conducted with 
      the approval of the ethics committee of Shanghai Jiao Tong University School of 
      Medicine and in accordance with the Animal Welfare & Ethics Committee of Shanghai 
      Jiao Tong University School of Medicine. COMPETING INTERESTS: The authors declare 
      that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains 
      neutral with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2018/06/17 06:00
MHDA- 2019/03/13 06:00
PMCR- 2018/06/15
CRDT- 2018/06/17 06:00
PHST- 2017/12/30 00:00 [received]
PHST- 2018/05/15 00:00 [accepted]
PHST- 2018/05/08 00:00 [revised]
PHST- 2018/06/17 06:00 [entrez]
PHST- 2018/06/17 06:00 [pubmed]
PHST- 2019/03/13 06:00 [medline]
PHST- 2018/06/15 00:00 [pmc-release]
AID - 10.1186/s13287-018-0905-2 [pii]
AID - 905 [pii]
AID - 10.1186/s13287-018-0905-2 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2018 Jun 15;9(1):164. doi: 10.1186/s13287-018-0905-2.