PMID- 31122700
OWN - NLM
STAT- MEDLINE
DCOM- 20200625
LR  - 20211204
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 515
IP  - 1
DP  - 2019 Jul 12
TI  - Decline of p300 contributes to cell senescence and growth inhibition of hUC-MSCs 
      through p53/p21 signaling pathway.
PG  - 24-30
LID - S0006-291X(19)30931-3 [pii]
LID - 10.1016/j.bbrc.2019.05.061 [doi]
AB  - Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in vitro 
      expansion for long term may undergo epigenetic and genetic alterations that 
      subsequently induce cellular senescence and associated growth inhibition. 
      Increasing evidence implicated that aberrant histone acetylation modulates gene 
      expression responsible for MSCs aging. Whether the dysregulation of p300 and its 
      KAT activity is involved in the aging process of MSCs was still unexplored. In 
      this study, we found a significant decrease of p300 but elevated p53/p21 levels 
      in senescent hUC-MSCs at late-passage. Then we used two different approaches: (i) 
      downregulation of p300 by siRNA and (ii) inhibition of the acetyltransferase(KAT) 
      activity by C646 to determine the role of p300 in regulating MSCs senescence. We 
      showed that inhibition of p300 induce premature senescence and decrease 
      proliferation potential in hUC-MSCs. Moreover, upregulations of p53 and p21 
      expressions were confirmed in p300 knockdown and C646-treated hUC-MSCs. Taken 
      together, these results suggest that p300 plays an important role in aging 
      process of MSCs associated with activation of p53/p21 signaling pathway.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Li, Yasha
AU  - Li Y
AD  - Pediatric Research Institute, Ministry of Education Key Laboratory of Child 
      Development and Disorders, Children's Hospital of Chongqing Medical University, 
      Chongqing, 400014, China; China International Science and Technology Cooperation 
      Base of Child Development and Critical Disorders, Chongqing, 400014, China; Stem 
      Cell Biology and Therapy Laboratory of Ministry of Education Key Laboratory for 
      Pediatrics, The Children's Hospital of Chongqing Medical University, Chongqing, 
      400014, China.
FAU - Zhong, Haiying
AU  - Zhong H
AD  - Pediatric Research Institute, Ministry of Education Key Laboratory of Child 
      Development and Disorders, Children's Hospital of Chongqing Medical University, 
      Chongqing, 400014, China; China International Science and Technology Cooperation 
      Base of Child Development and Critical Disorders, Chongqing, 400014, China.
FAU - Wu, Mengyun
AU  - Wu M
AD  - Pediatric Research Institute, Ministry of Education Key Laboratory of Child 
      Development and Disorders, Children's Hospital of Chongqing Medical University, 
      Chongqing, 400014, China; China International Science and Technology Cooperation 
      Base of Child Development and Critical Disorders, Chongqing, 400014, China; 
      Chongqing Stem Cell Therapy Engineering and Technology Center, Chongqing, 400014, 
      China.
FAU - Tan, Bin
AU  - Tan B
AD  - Pediatric Research Institute, Ministry of Education Key Laboratory of Child 
      Development and Disorders, Children's Hospital of Chongqing Medical University, 
      Chongqing, 400014, China; China International Science and Technology Cooperation 
      Base of Child Development and Critical Disorders, Chongqing, 400014, China.
FAU - Zhao, Li
AU  - Zhao L
AD  - Pediatric Research Institute, Ministry of Education Key Laboratory of Child 
      Development and Disorders, Children's Hospital of Chongqing Medical University, 
      Chongqing, 400014, China; China International Science and Technology Cooperation 
      Base of Child Development and Critical Disorders, Chongqing, 400014, China.
FAU - Yi, Qin
AU  - Yi Q
AD  - Pediatric Research Institute, Ministry of Education Key Laboratory of Child 
      Development and Disorders, Children's Hospital of Chongqing Medical University, 
      Chongqing, 400014, China.
FAU - Xu, Xiaohui
AU  - Xu X
AD  - Pediatric Research Institute, Ministry of Education Key Laboratory of Child 
      Development and Disorders, Children's Hospital of Chongqing Medical University, 
      Chongqing, 400014, China; China International Science and Technology Cooperation 
      Base of Child Development and Critical Disorders, Chongqing, 400014, China.
FAU - Pan, Huafeng
AU  - Pan H
AD  - Chongqing Stem Cell Therapy Engineering and Technology Center, Chongqing, 400014, 
      China.
FAU - Bi, Yang
AU  - Bi Y
AD  - Pediatric Research Institute, Ministry of Education Key Laboratory of Child 
      Development and Disorders, Children's Hospital of Chongqing Medical University, 
      Chongqing, 400014, China; China International Science and Technology Cooperation 
      Base of Child Development and Critical Disorders, Chongqing, 400014, China; Stem 
      Cell Biology and Therapy Laboratory of Ministry of Education Key Laboratory for 
      Pediatrics, The Children's Hospital of Chongqing Medical University, Chongqing, 
      400014, China.
FAU - Yang, Ke
AU  - Yang K
AD  - Pediatric Research Institute, Ministry of Education Key Laboratory of Child 
      Development and Disorders, Children's Hospital of Chongqing Medical University, 
      Chongqing, 400014, China; China International Science and Technology Cooperation 
      Base of Child Development and Critical Disorders, Chongqing, 400014, China; 
      Chongqing Stem Cell Therapy Engineering and Technology Center, Chongqing, 400014, 
      China. Electronic address: yangke@hospital.cqmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190520
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 
      (4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic 
      acid)
RN  - 0 (Benzoates)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Nitrobenzenes)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrazolones)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.1.48 (E1A-Associated p300 Protein)
RN  - EC 2.3.1.48 (EP300 protein, human)
SB  - IM
MH  - Benzoates/pharmacology
MH  - Cell Culture Techniques
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - *Cellular Senescence/drug effects
MH  - Cyclin-Dependent Kinase Inhibitor p21/*metabolism
MH  - E1A-Associated p300 Protein/antagonists & 
      inhibitors/*deficiency/genetics/metabolism
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - Nitrobenzenes
MH  - Pyrazoles/pharmacology
MH  - Pyrazolones
MH  - *Signal Transduction/drug effects
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Umbilical Cord/*cytology
OTO - NOTNLM
OT  - C646 inhibitor
OT  - Cellular senescence
OT  - hUC-MSCs
OT  - p300
OT  - p53/p21 signaling pathway
EDAT- 2019/05/28 06:00
MHDA- 2020/06/26 06:00
CRDT- 2019/05/25 06:00
PHST- 2019/05/05 00:00 [received]
PHST- 2019/05/07 00:00 [accepted]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2020/06/26 06:00 [medline]
PHST- 2019/05/25 06:00 [entrez]
AID - S0006-291X(19)30931-3 [pii]
AID - 10.1016/j.bbrc.2019.05.061 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Jul 12;515(1):24-30. doi: 
      10.1016/j.bbrc.2019.05.061. Epub 2019 May 20.