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Pharmacol Rep ; 67(6): 1103-14, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26481528

RESUMO

BACKGROUND: Several evidences indicate stimulation of peroxisome proliferator activated receptor γ (PPARg), promotes neuronal differentiation. This study was conducted to testify the prominence of PPARγ during neural differentiation of human embryonic stem cells (hESCs). METHODS: PPARγ expression level was assessed during neural differentiation of hESCs. Meanwhile, the level of endogenous miRNAs, which could be engaged in regulation of PPARγ expression, was measured. Next, natural and synthetic components of PPARγ agonists and antagonist were implemented on neural progenitor formation during neural differentiation of hESCs. RESULTS: Data showed an increasing wave of PPARγ expression level when human neural progenitors (NPs) were formed upon retinoic acid treatment. Interestingly, there was no significant difference in the amount of PPARγ proteins during the differentiation of hESCs that is inconsistent with what we observed for RNA level. Our results indicated that miRNAs are not involved in the regulation of PPARγ expression, while proteasome-mediated degradation may to some degree be involved in this process. Among numerous treatments, PPARγ inactivation during NPs formation significantly decreased expression of NP markers. CONCLUSIONS: We conclude that a ground state of PPARγ activity is required for NP formation of hESCs during early neural differentiation. However, high expression and activity of PPARγ could not enhance the required neural differentiation, whereas the PPARγ inactivation could negatively influence NP formation from hESCs by antagonist.


Assuntos
Células-Tronco Embrionárias Humanas/citologia , Células-Tronco Neurais/citologia , Neurogênese , PPAR gama/metabolismo , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Humanos , Leupeptinas/farmacologia , MicroRNAs/fisiologia , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , PPAR gama/agonistas , PPAR gama/biossíntese , Complexo de Endopeptidases do Proteassoma/fisiologia , Tretinoína/farmacologia
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