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Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 328-334, 2016.
Artigo em Inglês | WPRIM | ID: wpr-285267

RESUMO

Thymosin β4 (Tβ4) is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells (mESCs) proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of Tβ4 on mESCs. Target genes during mESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the mESCs-derived cardiomyocytes. It was found that Tβ4 decreased mESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c-myc, c-fos and c-jun. However, mESCs self-renewal markers Oct4 and Nanog were elevated, indicating the maintenance of self-renewal ability in these mESCs. Phosphorylation of STAT3 and Akt was inhibited by Tβ4 while the expression of RAS and phosphorylation of ERK were enhanced. No significant difference was found in BMP2/BMP4 or their downstream protein smad. Wnt3 and Wnt11 were remarkably decreased by Tβ4 with upregulation of Tcf3 and constant β-catenin. Under mESCs differentiation, Tβ4 treatment did not change the expression of cardiovascular cell markers α-MHC, PECAM, and α-SMA. Neither the electrophysiological properties of mESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by Tβ4. In conclusion, Tβ4 suppressed mESCs proliferation by affecting the activity of STAT3, Akt, ERK and Wnt pathways. However, Tβ4 did not influence the in vitro cardiovascular differentiation.


Assuntos
Animais , Camundongos , Ciclo Celular , Genética , Diferenciação Celular , Movimento Celular , Proliferação de Células , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular , Genética , Metabolismo , Regulação da Expressão Gênica , Proteínas Quinases JNK Ativadas por Mitógeno , Genética , Metabolismo , Células-Tronco Embrionárias Murinas , Biologia Celular , Metabolismo , Miócitos Cardíacos , Biologia Celular , Metabolismo , Proteína Homeobox Nanog , Genética , Metabolismo , Fator 3 de Transcrição de Octâmero , Genética , Metabolismo , Técnicas de Patch-Clamp , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt , Genética , Metabolismo , Proteínas Proto-Oncogênicas c-fos , Genética , Metabolismo , Proteínas Proto-Oncogênicas c-myc , Genética , Metabolismo , Fator de Transcrição STAT3 , Genética , Metabolismo , Transdução de Sinais , Timosina , Farmacologia
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