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学科主题临床医学
Ghrelin induces cardiac lineage differentiation of human embryonic stem cells through ERK1/2 pathway
Gao, Meijuan1,3; Yang, Jin1,3; Wei, Rui1,3; Liu, Guoqiang1,3; Zhang, Lin1,3; Wang, Haining1,3; Wang, Guang1,3; Gao, Hongwei1,3; Chen, Guian2,3; Hong, Tianpei1,3
关键词Human embryonic stem cells Ghrelin Differentiation Cardiomyocytes
刊名INTERNATIONAL JOURNAL OF CARDIOLOGY
2013-09-10
DOI10.1016/j.ijcard.2012.06.106
167期:6页:2724-2733
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems
资助者National Natural Science Foundations of China ; Chinese National 863 Program ; Chinese National 973 Program ; Specialized Research Fund for the Doctoral Program of Higher Education ; National Natural Science Foundations of China ; Chinese National 863 Program ; Chinese National 973 Program ; Specialized Research Fund for the Doctoral Program of Higher Education
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]CARDIOMYOCYTE DIFFERENTIATION ; HEART-FAILURE ; BLASTOCYSTS ; SOX9 ; CARDIOMYOGENESIS ; TRANSCRIPTION ; PROGENITORS ; DYSFUNCTION ; POPULATION ; INHIBITOR
英文摘要

Background: Ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R), shows cardioprotective activity and regulates the differentiation of several mesoderm-derived cells, including myocytes, adipocytes and osteoblasts. The effect of ghrelin on cardiogenesis and its underlying mechanism, however, have not been studied in detail.

Methods: The effects of ghrelin on cardiomyocyte differentiation were tested both in human embryonic stem cells (hESCs) cultured in embryoid body (EB)-based differentiation protocol, and in hESCs transplanted into rat hearts. The signaling mechanisms of ghrelin were further investigated under the EB-based culture condition.

Results: The generation of beating EBs and the expression of cardiac-specific markers including cardiac troponin I (cTnI) and alpha-myosin heavy chain (alpha-MHC) were 2 to 3-fold upregulated by ghrelin. Although GHS-R1 alpha protein was expressed in differentiated EBs, the effects of exogenous ghrelin were unchanged by D-[lys(3)]-GHRP-6, a specific GHS-R1 alpha antagonist. Moreover, des-acyl ghrelin, which does not bind to GHS-R1 alpha, displayed similar effects with ghrelin. Importantly, activation of ERK1/2, but not Akt, was induced by ghrelin in the newly-formed EBs, and the ghrelin-induced effects of cardiomyocyte differentiation were abolished by adding specific ERK1/2 inhibitor PD98059, but not specific PI3K inhibitor Wortmannin. In addition, ghrelin promoted the differentiation of grafted hESCs into Sox9- and Flk1-positive mesodermal/cardiac progenitor cells in rat hearts.

Conclusions: These results suggest that ghrelin induces cardiomyocyte differentiation from hESCs via the activation of the ERK1/2 signaling pathway. Our study, therefore, indicates that using ghrelin may be an effective strategy to promote the differentiation of hESCs into cardiomyocytes. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

语种英语
所属项目编号30771032 ; 30700879 ; 81070701 ; 81000315 ; 2006AA02A112 ; 2012CB517502 ; 20100001110083
资助者National Natural Science Foundations of China ; Chinese National 863 Program ; Chinese National 973 Program ; Specialized Research Fund for the Doctoral Program of Higher Education ; National Natural Science Foundations of China ; Chinese National 863 Program ; Chinese National 973 Program ; Specialized Research Fund for the Doctoral Program of Higher Education
WOS记录号WOS:000324478400068
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63163
专题北京大学第三临床医学院
作者单位1.Peking Univ, Hosp 3, Dept Endocrinol & Metab, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Reprod Med Ctr, Beijing 100191, Peoples R China
3.Peking Univ, Hosp 3, Clin Stem Cell Res Ctr, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Gao, Meijuan,Yang, Jin,Wei, Rui,et al. Ghrelin induces cardiac lineage differentiation of human embryonic stem cells through ERK1/2 pathway[J]. INTERNATIONAL JOURNAL OF CARDIOLOGY,2013,167(6):2724-2733.
APA Gao, Meijuan.,Yang, Jin.,Wei, Rui.,Liu, Guoqiang.,Zhang, Lin.,...&Hong, Tianpei.(2013).Ghrelin induces cardiac lineage differentiation of human embryonic stem cells through ERK1/2 pathway.INTERNATIONAL JOURNAL OF CARDIOLOGY,167(6),2724-2733.
MLA Gao, Meijuan,et al."Ghrelin induces cardiac lineage differentiation of human embryonic stem cells through ERK1/2 pathway".INTERNATIONAL JOURNAL OF CARDIOLOGY 167.6(2013):2724-2733.
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