PMID- 31340157
OWN - NLM
STAT- MEDLINE
DCOM- 20200824
LR  - 20200824
IS  - 2211-1247 (Electronic)
VI  - 28
IP  - 4
DP  - 2019 Jul 23
TI  - PDGFR-beta Signaling Regulates Cardiomyocyte Proliferation and Myocardial 
      Regeneration.
PG  - 966-978.e4
LID - S2211-1247(19)30845-9 [pii]
LID - 10.1016/j.celrep.2019.06.065 [doi]
AB  - Platelet-derived growth factor receptor (PDGFR) signaling is involved in 
      proliferation and survival in a wide array of cell types. The role of PDGFR 
      signaling in heart regeneration is still unknown. We find that PDGFR-beta signaling 
      decreases in myocardium with age and that conditional activation PDGFR-beta in 
      cardiomyocytes promotes heart regeneration. Employing RNA sequencing, we show 
      that the enhancer of zeste homolog 2 (Ezh2) can be upregulated by PDGFR-beta 
      signaling in primary cardiomyocytes. Conditional knockout of Ezh2 blocks 
      cardiomyocyte proliferation and H3K27me3 modification during neonatal heart 
      regeneration with Ink4a/Arf upregulation, even in mice with myocyte-specific 
      conditional activation of PDGFR-beta. We also show that PDGFR-beta controls EZH2 
      expression via the phosphatidylinositol 3-kinase (PI3K)/p-Akt pathway in 
      cardiomyocytes. Gene therapy with adeno-associated virus serotype 9 (AAV9) 
      encoding activated PDGFR-beta enhances adult heart regeneration and systolic 
      function. Our data demonstrate that the PDGFR-beta/EZH2 pathway is critical for 
      promoting cardiomyocyte proliferation and heart regeneration, providing a 
      potential target for cardiac repair.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Yue, Zhang
AU  - Yue Z
AD  - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China; State Key 
      Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for 
      Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China.
FAU - Chen, Jiuling
AU  - Chen J
AD  - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China; State Key 
      Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for 
      Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China.
FAU - Lian, Hong
AU  - Lian H
AD  - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center 
      for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China.
FAU - Pei, Jianqiu
AU  - Pei J
AD  - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center 
      for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China.
FAU - Li, Yandong
AU  - Li Y
AD  - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center 
      for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China.
FAU - Chen, Xianda
AU  - Chen X
AD  - Children's Heart Center, the Second Affiliated Hospital & Yuying Children's 
      Hospital, Institute of Cardiovascular Development and Translational Medicine, 
      Wenzhou Medical University, Wenzhou 325027, China.
FAU - Song, Shen
AU  - Song S
AD  - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center 
      for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China.
FAU - Xia, Jiahong
AU  - Xia J
AD  - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Zhou, Bin
AU  - Zhou B
AD  - State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell 
      Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of 
      Sciences (CAS), University of Chinese Academy of Sciences, Shanghai 200031, 
      China.
FAU - Feng, Jie
AU  - Feng J
AD  - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center 
      for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China.
FAU - Zhang, Xinyue
AU  - Zhang X
AD  - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center 
      for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China.
FAU - Hu, Shengshou
AU  - Hu S
AD  - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China; State Key 
      Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for 
      Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China. Electronic address: 
      shengshouhu@yahoo.com.
FAU - Nie, Yu
AU  - Nie Y
AD  - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center 
      for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100037, China. Electronic address: 
      nieyu@fuwaihospital.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cell Proliferation
MH  - Enhancer of Zeste Homolog 2 Protein/metabolism
MH  - Mice, Inbred C57BL
MH  - Myocardial Infarction/metabolism/pathology
MH  - Myocardium/*metabolism
MH  - Myocytes, Cardiac/*cytology/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, Platelet-Derived Growth Factor beta/*metabolism
MH  - *Regeneration
MH  - *Signal Transduction
OTO - NOTNLM
OT  - AAV9
OT  - Ezh2
OT  - PDGFR-beta
OT  - cardiac repair
OT  - cardiomyocyte proliferation
OT  - heart regeneration
EDAT- 2019/07/25 06:00
MHDA- 2020/08/25 06:00
CRDT- 2019/07/25 06:00
PHST- 2017/12/14 00:00 [received]
PHST- 2019/04/24 00:00 [revised]
PHST- 2019/06/18 00:00 [accepted]
PHST- 2019/07/25 06:00 [entrez]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2020/08/25 06:00 [medline]
AID - S2211-1247(19)30845-9 [pii]
AID - 10.1016/j.celrep.2019.06.065 [doi]
PST - ppublish
SO  - Cell Rep. 2019 Jul 23;28(4):966-978.e4. doi: 10.1016/j.celrep.2019.06.065.