miRNA let-7e targeting MMP9 is involved in adipose-derived stem cell differentiation toward epithelia

miRNA let-7e is involved in stem cell differentiation, and metalloproteinases are among its potential target genes. We hypothesized that the inhibitory action of let-7e on regulation of MMP9 expression could represent a crucial mechanism during differentiation of adipose-derived stem cells (ASCs). A...

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Detalhes bibliográficos
Autores: Ventayol Espinazo, Marina, Viñas Muñoz, José Luis, Sola Martínez, Anna, Jung, Michaela, Brüne, Bernhard, 1957-, Pi i Siqués, Felip, Mastora, Chrysoula, Hotter Corripio, Georgina
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/133452
Acesso em linha:https://hdl.handle.net/2445/133452
Access Level:acceso abierto
Palavra-chave:Obesitat
Citologia
Enzimologia
Genètica
Cèl·lules mare
Obesity
Cytology
Enzymology
Genetics
Stem cells
Descrição
Resumo:miRNA let-7e is involved in stem cell differentiation, and metalloproteinases are among its potential target genes. We hypothesized that the inhibitory action of let-7e on regulation of MMP9 expression could represent a crucial mechanism during differentiation of adipose-derived stem cells (ASCs). ASCs were differentiated with all-trans retinoic acid (ATRA) to promote differentiation, and the effect of let-7 silencing during differentiation was tested. Results indicate that ASCs cultured with ATRA differentiated into cells of the epithelial lineage. We found that ASCs cultured with ATRA or transfected with miRNA let-7e expressed epithelial markers such as cytokeratin-18 and early renal organogenesis markers such as Pax2, Wt1, Wnt4 and megalin. Conversely, the specific knockdown of miRNA let-7e in ASCs significantly decreased the expression of these genes, indicating its vital role during the differentiation process. Using luciferase reporter assays, we also showed that MMP9 is a direct target of miRNA let-7e. Thus, our results suggest that miRNA let-7e acts as a matrix metalloproteinase-9 (MMP9) inhibitor and differentiation inducer in ASCs.

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