title: miR-145 inhibits isoproterenol-induced cardiomyocyte hypertrophy by targeting the expression and localization of GATA6.
abstract: Excessive βAR stimulation is an independent factor in inducing pathological cardiac hypertrophy. Here, we report miR-145 regulates both expression and localization of GATA6, thereby protecting the heart against cardiomyocyte hypertrophy induced by isoproterenol (ISO). The protective activity of miR-145 was associated with down-regulation of ANF, BNP and β-MHC expression, a decreased rate of protein synthesis, inhibited cardiomyocyte growth and the modulation of several signaling pathways including ERK1/2, JNK and Akt-GSK3β. The anti-hypertrophic effect was abrogated by exogenous over-expression of transcription factor GATA6 which was further identified as a direct target of miR-145. In addition, GSK3β antagonists, LiCl and TDZD8, restored the nuclear accumulation of GATA6, which was attenuated by miR-145 Finally, we observed a dynamic pattern of miR-145 expression in ISO-treated NRCMs and in the hearts of TAC mice. Together, our results identify miR-145 as an important regulator in cardiac hypertrophy.
authors.affiliation: Department of Cardiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People's Republic of China.
authors.forename: Ruotian
authors.initials: R
authors.lastname: Li
authors.forename: Guijun
authors.initials: G
authors.lastname: Yan
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.forename: Haixiang
authors.initials: H
authors.lastname: Sun
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Sun
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006984:Hypertrophy / Q000139:chemically induced / Q000235:genetics; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020413:3' Untranslated Regions; D000318:Adrenergic beta-Agonists; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D007545:Isoproterenol