title: Overexpression of Tbx20 in Adult Cardiomyocytes Promotes Proliferation and Improves Cardiac Function After Myocardial Infarction.
abstract: BACKGROUND
  Adult mammalian cardiomyocytes (CMs) have the potential to proliferate, but this is not sufficient to generate adequate CMs after myocardial infarction (MI). The transcription factor Tbx20 is required for CM proliferation during development and adult CM homeostasis. The ability of Tbx20 overexpression (Tbx20(OE)) to promote adult CM proliferation and to improve cardiac function after MI was examined.
  
  
  RESULTS
  Tbx20(OE) was induced specifically in adult mouse differentiated CMs. Increased CM proliferation and fetal-like characteristics were found in Tbx20(OE) hearts compared with controls without causing pathology 4 weeks after Tbx20(OE) at baseline. Moreover, Tbx20(OE) in adult CM after MI significantly improved survival, cardiac function, and infarct size 4 weeks after MI. Improved cardiac repair, as indicated by increased CM proliferation and capillary density, was observed in the MI border zone of Tbx20(OE) hearts compared with controls. Expression of proliferation activator (cyclin D1, E1, and IGF1) and fetal contractile protein (ssTNI, βMHC) mRNA was increased whereas negative cell-cycle regulators (p21, Meis1) were decreased in Tbx20(OE) hearts compared with controls under both baseline and MI conditions. Tbx20(OE) in adult hearts activates multiple proproliferation pathways, including Akt, YAP and BMP. Interestingly, p21, Meis1, and a novel cell-cycle inhibitory gene, Btg2, are directly bound and repressed by Tbx20 with induction of proliferation in neonatal CM.
  
  
  CONCLUSIONS
  Tbx20(OE), specifically in adult CM, activates multiple cardiac proliferative pathways, directly represses cell-cycle inhibitory genes p21, Meis1, and Btg2, promotes adult CM proliferation; and preserves cardiac performance after MI.
authors: From Heart Institute, Cincinnati Children's Medical Center, OH (F.-l.X., K.E.Y.); and Department of Electrical Engineering and Computing Systems, University of Cincinnati, OH (M.G.).
authors: Fu-Li
authors: FL
authors: Xiang
authors: From Heart Institute, Cincinnati Children's Medical Center, OH (F.-l.X., K.E.Y.); and Department of Electrical Engineering and Computing Systems, University of Cincinnati, OH (M.G.).
authors: Minzhe
authors: M
authors: Guo
authors: From Heart Institute, Cincinnati Children's Medical Center, OH (F.-l.X., K.E.Y.); and Department of Electrical Engineering and Computing Systems, University of Cincinnati, OH (M.G.). katherine.yutzey@cchmc.org.
authors: Katherine E
authors: KE
authors: Yutzey
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division; D048429:Cell Size / Q000187:drug effects; D004562:Electrocardiography; D005260:Female; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D018816:Genes, cdc / Q000187:drug effects; D006321:Heart / Q000503:physiopathology; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D016037:Single-Blind Method; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
chemical_list: C489435:Btg2 protein, mouse; D018797:Cell Cycle Proteins; D005326:Fetal Proteins; D017874:Immediate-Early Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020825:T-Box Domain Proteins; C486013:Tbx20 protein, mouse; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen
keywords: cell cycle; molecular biology; myocardial infarction; myocytes, cardiac; regeneration