PMID- 26111576
OWN - NLM
STAT- MEDLINE
DCOM- 20160328
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 36
IP  - 3
DP  - 2015
TI  - Autophagy is Required for the Maintenance of Liver Progenitor Cell Functionality.
PG  - 1163-74
LID - 10.1159/000430287 [doi]
AB  - BACKGROUND: Liver progenitor cells (LPCs) are bipotent stem cells existing in the 
      adult liver, which could be activated upon massive liver injury and contribute to 
      liver regeneration. However, mechanisms of maintenance of LPC functionality 
      remain poorly understood. Previous studies found that autophagy was required for 
      the self-renewal and differentiation of several tissue stem cells. METHODS: The 
      study compared the level of autophagic activity in LPCs and differentiated 
      hepatocytes. Then, autophagic activity was inhibited in LPCs by 
      lentivirus-mediated autophagy-related gene 5 or Beclin 1 knockdown. Clonogenic 
      assay, cell viability assays, hepatic differentiation assay, and senescence 
      analysis were conducted to assess the role of autophagy in regulating 
      self-renewal, hepatic differentiation and senescence of LPCs. RESULTS: We 
      observed high autophagic activity in LPCs compared with differentiated 
      hepatocytes. We found that inhibition of autophagy impaired the self-renewal, 
      proliferation, and hepatic differentiation capability of LPCs under normal 
      cultural condition, but had little impact on cell viability. Interestingly, while 
      wild-type LPCs remained rarely affected by the toxin, etoposide, inhibition of 
      autophagy induced the senescent phenotype of LPCs. Overexpression of Beclin 1 in 
      Beclin 1-knockdown LPCs restored the functionality of stem cells. CONCLUSION: Our 
      findings indicate that autophagy may function as a critical regulator of LPC 
      functionality under both physiological and pathological condition.
CI  - (c) 2015 S. Karger AG, Basel.
FAU - Cheng, Yiji
AU  - Cheng Y
AD  - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao 
      Tong University School of Medicine, Shanghai, China.
FAU - Wang, Bei
AU  - Wang B
FAU - Zhou, Hong
AU  - Zhou H
FAU - Dang, Shipeng
AU  - Dang S
FAU - Jin, Min
AU  - Jin M
FAU - Shi, Yufang
AU  - Shi Y
FAU - Hao, Li
AU  - Hao L
FAU - Yang, Zhenxi
AU  - Yang Z
FAU - Zhang, Yanyun
AU  - Zhang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150625
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Atg5 protein, mouse)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 6PLQ3CP4P3 (Etoposide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Apoptosis Regulatory Proteins/antagonists & inhibitors/*genetics/metabolism
MH  - Autophagy/drug effects/*genetics
MH  - Autophagy-Related Protein 5
MH  - Beclin-1
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Etoposide/pharmacology
MH  - Gene Expression
MH  - Hepatocytes/cytology/drug effects/metabolism
MH  - Liver Regeneration/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microtubule-Associated Proteins/antagonists & inhibitors/genetics/metabolism
MH  - Primary Cell Culture
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Stem Cells/cytology/drug effects/*metabolism
EDAT- 2015/06/27 06:00
MHDA- 2016/03/29 06:00
CRDT- 2015/06/27 06:00
PHST- 2015/04/10 00:00 [accepted]
PHST- 2015/06/27 06:00 [entrez]
PHST- 2015/06/27 06:00 [pubmed]
PHST- 2016/03/29 06:00 [medline]
AID - 000430287 [pii]
AID - 10.1159/000430287 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2015;36(3):1163-74. doi: 10.1159/000430287. Epub 2015 Jun 
      25.