title: Beta-adrenergic signals regulate cardiac differentiation of mouse embryonic stem cells via mitogen-activated protein kinase pathways.
abstract: As embryonic stem cell-derived cardiomyocytes (ESC-CMs) have the potential to be used in cell replacement therapy, an understanding of the signaling mechanisms that regulate their terminal differentiation is imperative. In previous studies, we discovered the presence of adrenergic and muscarinic receptors in mouse embryonic stem cells (ESCs). However, little is known about the role of these receptors in cardiac differentiation and development, which is critically important in cardiac physiology and pharmacology. Here, we demonstrated that a β-adrenergic receptor (β-AR) agonist significantly enhanced cardiac differentiation as indicated by a higher percentage of beating embryoid bodies and a higher expression level of cardiac markers. Application of β1-AR and β2-AR antagonists partly abolished the effect of the β-AR agonist. In addition, by administering selective inhibitors we found that the effect of β-AR was driven via p38 mitogen-activated protein kinase and extracellular-signal regulated kinase pathway. These findings suggest that ESCs are also a target for β-adrenergic regulation and β-adrenergic signaling plays a role in ESC cardiac differentiation.
authors.affiliation: Department of Cardiology, Peking University Third Hospital, Haidian District, Beijing, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Yan
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Jia
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cui
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yang
authors.forename: Huangtian
authors.initials: H
authors.lastname: Yang
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D007545:Isoproterenol / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D051379:Mice; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011433:Propranolol / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C547788:Adrb1 protein, mouse; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D020107:Troponin T; D011433:Propranolol; D048051:p38 Mitogen-Activated Protein Kinases; D007545:Isoproterenol