PMID- 26893347
OWN - NLM
STAT- MEDLINE
DCOM- 20160801
LR  - 20160316
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Linking)
VI  - 143
IP  - 6
DP  - 2016 Mar 15
TI  - GATA4 regulates Fgf16 to promote heart repair after injury.
PG  - 936-49
LID - 10.1242/dev.130971 [doi]
AB  - Although the mammalian heart can regenerate during the neonatal stage, this 
      endogenous regenerative capacity is lost with age. Importantly, replication of 
      cardiomyocytes has been found to be the key mechanism responsible for neonatal 
      cardiac regeneration. Unraveling the transcriptional regulatory network for 
      inducing cardiomyocyte replication will, therefore, be crucial for the 
      development of novel therapies to drive cardiac repair after injury. Here, we 
      investigated whether the key cardiac transcription factor GATA4 is required for 
      neonatal mouse heart regeneration. Using the neonatal mouse heart cryoinjury and 
      apical resection models with an inducible loss of GATA4 specifically in 
      cardiomyocytes, we found severely depressed ventricular function in the 
      Gata4-ablated mice (mutant) after injury. This was accompanied by reduced 
      cardiomyocyte replication. In addition, the mutant hearts displayed impaired 
      coronary angiogenesis and increased hypertrophy and fibrosis after injury. 
      Mechanistically, we found that the paracrine factor FGF16 was significantly 
      reduced in the mutant hearts after injury compared with littermate controls and 
      was directly regulated by GATA4. Cardiac-specific overexpression of FGF16 via 
      adeno-associated virus subtype 9 (AAV9) in the mutant hearts partially rescued 
      the cryoinjury-induced cardiac hypertrophy, promoted cardiomyocyte replication 
      and improved heart function after injury. Altogether, our data demonstrate that 
      GATA4 is required for neonatal heart regeneration through regulation of Fgf16, 
      suggesting that paracrine factors could be of potential use in promoting 
      myocardial repair.
CI  - (c) 2016. Published by The Company of Biologists Ltd.
FAU - Yu, Wei
AU  - Yu W
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Huang, Xiuzhen
AU  - Huang X
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Tian, Xueying
AU  - Tian X
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - He, Lingjuan
AU  - He L
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
FAU - Wang, Yue
AU  - Wang Y
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
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.
FAU - Hu, Shengshou
AU  - Hu 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 - Lin, Zhiqiang
AU  - Lin Z
AD  - Department of Cardiology, Boston Children's Hospital, 300 Longwood Ave, Boston, 
      MA 02115, USA.
FAU - Zhou, Bin
AU  - Zhou B
AD  - Departments of Genetics, Pediatrics and Medicine (Cardiology), Albert Einstein 
      College of Medicine of Yeshiva University, 1301 Morris Park Avenue, Bronx, NY 
      10461, USA.
FAU - Pu, William
AU  - Pu W
AD  - Department of Cardiology, Boston Children's Hospital, 300 Longwood Ave, Boston, 
      MA 02115, USA.
FAU - Lui, Kathy O
AU  - Lui KO
AD  - Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The 
      Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, 
      999077 China.
FAU - Zhou, Bin
AU  - Zhou B
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 
      Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for 
      Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for 
      Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China School 
      of Life Science and Technology, ShanghaiTech University, Shanghai, 201210 China 
      zhoubin@sibs.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160218
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Fgf16 protein, mouse)
RN  - 0 (GATA4 Transcription Factor)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Base Sequence
MH  - Cell Proliferation
MH  - Dependovirus/metabolism
MH  - Fibroblast Growth Factors/*metabolism
MH  - GATA4 Transcription Factor/*metabolism
MH  - Gene Deletion
MH  - Heart/*physiopathology
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Mutation/genetics
MH  - Myocytes, Cardiac/metabolism/pathology
MH  - Neovascularization, Physiologic
MH  - Organ Specificity
MH  - Phenotype
MH  - *Regeneration
OTO - NOTNLM
OT  - Cardiomyocyte proliferation
OT  - FGF16
OT  - GATA4
OT  - Heart regeneration
OT  - Heart repair
EDAT- 2016/02/20 06:00
MHDA- 2016/08/02 06:00
CRDT- 2016/02/20 06:00
PHST- 2015/09/14 00:00 [received]
PHST- 2016/02/09 00:00 [accepted]
PHST- 2016/02/20 06:00 [entrez]
PHST- 2016/02/20 06:00 [pubmed]
PHST- 2016/08/02 06:00 [medline]
AID - dev.130971 [pii]
AID - 10.1242/dev.130971 [doi]
PST - ppublish
SO  - Development. 2016 Mar 15;143(6):936-49. doi: 10.1242/dev.130971. Epub 2016 Feb 
      18.