title: Meis1 promotes poly (rC)-binding protein 2 expression and inhibits angiotensin II-induced cardiomyocyte hypertrophy.
abstract: The poly(rC)-binding protein 2 (PCBP2) is currently reported to inhibit cardiac hypertrophy. However, how PCBP2 is regulated at transcriptional level remains unknown. Here, we show that Meis1, a PBX1-related homeobox gene, binds to PCBP2 promoter and promotes its transcription. In human failing heart tissues and murine hypertrophic heart tissues, the mRNA and protein levels of Meis1 are markedly downregulated, and the level of Meis1 significantly correlates with levels of Nppa, Myh7, and PCBP2. In neonatal rat cardiomyocytes, angiotensin II (Ang II) treatment induces hypertrophic growth of the cells (increase in cell size, enhanced protein synthesis, and hyperexpression of hypertrophic fetal genes), which are significantly inhibited by Meis1 overexpression or promoted by Meis1 knockdown. Meis1 also reduces Ang II-induced activation of Akt-mTOR pathway. Finally, we show that PCBP2 overexpression rescues the Meis1 effects of Akt-mTOR pathway and hypertrophy of cardiomyocytes. © 2015 IUBMB Life, 68(1):13-22, 2016.
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yunjiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Si
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
mesh_terms: D000804:Angiotensin II; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D008810:Mice, Inbred C57BL; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D032383:Myocytes, Cardiac / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C501904:Pcbp2 protein, mouse; D016601:RNA-Binding Proteins; D000804:Angiotensin II; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Meis1, PCBP2; angiotensin II; cardiomyocyte hypertrophy