RESUMEN
Recent findings indicate that microRNAs (miRNAs) are critical for the regulatory network of adipogenesis in human mesenchymal stem/stromal cells (MSCs). Fetal MSCs derived from amniotic fluid (AF-MSCs) represent a population of multipotent stem cells characterized by a wide range of differentiation properties that can be applied in cell-based therapies. In this study, miRNA microarray analysis was performed to assess miRNA expression in terminal differentiated AF-MSCs into adipocyte-like cells (AL cells). MiR-26a was identified in high expression levels in AL cells indicating a critical role in the process of adipogenesis. Overexpression of miR-26a in AF-MSCs led to significant induction of their adipogenic differentiation properties that were altered after miR-26a inhibition. We have demonstrated that miR-26a regulates adipogenesis through direct inhibition of PTEN, which in turn promotes activation of Akt pathway. Also, miR-26a modulates cell cycle during adipogenesis by interacting with Cyclin E1 and CDK6. These results point to the regulatory role of miR-26a and its target genes PTEN, Cyclin E1, and CDK6 in adipogenic differentiation of AF-MSCs, providing a basis for understanding the mechanisms of fat cell development and obesity.
Asunto(s)
Adipogénesis/genética , Ciclina E/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Células Madre Mesenquimatosas/citología , MicroARNs/genética , Células Madre Multipotentes/citología , Proteínas Oncogénicas/metabolismo , Fosfohidrolasa PTEN/metabolismo , Adipocitos/citología , Tejido Adiposo/citología , Líquido Amniótico/metabolismo , Células Cultivadas , Humanos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/genéticaRESUMEN
Many phenotypic changes of eukaryotic cells due to changes in gene expression depend on alterations in chromatin structure. Processes involved in the alteration of chromatin are diverse and include post-translational modifications of histone proteins, incorporation of specific histone variants, methylation of DNA and ATP-dependent chromatin remodeling. Interconnected with these processes are the localization of chromatin domains within the nuclear architecture and the appearance of various classes of noncoding regulatory RNAs. Recent experiments underscore the role of these processes in influencing diverse biological functions. However, the evidence to date implies the importance of an interplay of all these chromatin-changing functions, generating an epigenetic regulatory circuit that is still not well understood.
