title: miR-199-sponge transgenic mice develop physiological cardiac hypertrophy.
abstract: OBJECTIVE
  Overexpression of either member of the miR-199 family, miR-199a-5p, or miR-199b-5p (hereinafter referred to as miR-199a or miR-199b) promotes pathological cardiac hypertrophy, but little is known about the role of endogenous miR-199 in cardiac development and disease. Our study aimed to determine the physiological function of the endogenous miR-199 family in cardiac homeostasis maintenance.
  
  
  RESULTS
  We generated a sponge transgenic mouse model with a specific disruption of miR-199 in the heart. To our surprise, we found that knockdown of endogenous miR-199 caused physiological cardiac hypertrophy characterized by an increased heart weight and cardiomyocyte size, but with normal cardiac morphology and function. Furthermore, we also identified PGC1α as the target gene of the miR-199 family, and PGC1α was also increased in sponge transgenic mice.
  
  
  CONCLUSIONS
  Inhibition of endogenous miR-199 led to physiological cardiac hypertrophy probably due to the up-regulation of PGC1α, uncovering a surprising role for endogenous miR-199 in the maintenance of cardiac homeostasis.
authors.affiliation: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, Beijing 100071, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, Beijing 100071, China.
authors.forename: Lantao
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, Beijing 100071, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Hou
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Song
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, China.
authors.forename: Xiangbo
authors.initials: X
authors.lastname: An
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, China.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, Beijing 100071, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, Beijing 100071, China wangjian7773@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C534780:Mirn199 microRNA, mouse; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse
keywords: Physiological cardiac hypertrophy; Transgenic mice; miR-199 family; miRNA sponge