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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. © 2014 Macmillan Publishers Limited.This work was supported by Plan Nacional Project (SAF 2012-39947-CO2 to GH) and Fondo de Investigación Sanitaria projects (FIS PS09/01288 and PI 12/00720 to AS). AS is supported by the Miguel Servet contracting system (CP08/00138). MV is supported by a grant from IDIBAPS (beques de formació de personal investigador Institut d’Investigacions Biomèdiques August Pi i Sunyer)Peer Reviewe

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