title: Apelin: an endogenous peptide essential for cardiomyogenic differentiation of mesenchymal stem cells via activating extracellular signal-regulated kinase 1/2 and 5.
abstract: Growing evidence has shown that apelin/APJ system functions as a critical mediator of cardiac development as well as cardiovascular function. Here, we investigated the role of apelin in the cardiomyogenic differentiation of mesenchymal stem cells derived from Wharton's jelly of human umbilical cord in vitro. In this research, we used RNA interference methodology and gene transfection technique to regulate the expression of apelin in Wharton's jelly-derived mesenchymal stem cells and induced cells with a effective cardiac differentiation protocol including 5-azacytidine and bFGF. Four weeks after induction, induced cells assumed a stick-like morphology and myotube-like structures except apelin-silenced cells and the control group. The silencing expression of apelin in Wharton's jelly-derived mesenchymal stem cells decreased the expression of several critical cardiac progenitor transcription factors (Mesp1, Mef2c, NKX2.5) and cardiac phenotypes (cardiac α-actin, β-MHC, cTnT, and connexin-43). Meanwhile, endogenous compensation of apelin contributed to differentiating into cells with characteristics of cardiomyocytes in vitro. Further experiment showed that exogenous apelin peptide rescued the cardiomyogenic differentiation of apelin-silenced mesenchymal stem cells in the early stage (1-4 days) of induction. Remarkably, our experiment indicated that apelin up-regulated cardiac specific genes in Wharton's jelly-derived mesenchymal stem cells via activating extracellular signal-regulated kinase (ERK) 1/2 and 5.
authors.affiliation: Cardiovascular Center, Navy General Hospital, Beijing, 100048, China.|Department of Internal Medicine, The 413th Hospital of P. L. A., Zhoushan, Zhejiang, 316000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cardiovascular Center, Navy General Hospital, Beijing, 100048, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zhu
authors.affiliation: Cardiovascular Center, Navy General Hospital, Beijing, 100048, China.
authors.forename: Ning-Kun
authors.initials: NK
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, The 413th Hospital of P. L. A., Zhoushan, Zhejiang, 316000, China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Fang
authors.affiliation: Cardiovascular Center, Navy General Hospital, Beijing, 100048, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Xu
authors.affiliation: Cardiovascular Center, Navy General Hospital, Beijing, 100048, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Cardiovascular Center, Navy General Hospital, Beijing, 100048, China.
authors.forename: Lian-Ru
authors.initials: LR
authors.lastname: Gao
mesh_terms: D000199:Actins / Q000378:metabolism; D000073861:Apelin; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000201:enzymology; D010766:Phosphorylation; D014157:Transcription Factors / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; C115436:APLN protein, human; D000199:Actins; D000073861:Apelin; D018031:Connexin 43; D036341:Intercellular Signaling Peptides and Proteins; D014157:Transcription Factors; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: apelin; cardiomyogenesis; extracellular signal-regulated kinase; human umbilical cord mesenchymal stem cells