title: miRNA let-7e targeting MMP9 is involved in adipose-derived stem cell differentiation toward epithelia.
abstract: 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.
authors: Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona, Spanish Research Council (IIBB-CSIC, IDIBAPS), Barcelona, Spain.
authors: M
authors: M
authors: Ventayol
authors: Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona, Spanish Research Council (IIBB-CSIC, IDIBAPS), Barcelona, Spain.
authors: J L
authors: JL
authors: Viñas
authors: 1] Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona, Spanish Research Council (IIBB-CSIC, IDIBAPS), Barcelona, Spain [2] CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Department of Experimental Pathology, IIBB-CSIC-IDIBAPS, Barcelona, Spain.
authors: A
authors: A
authors: Sola
authors: Institute of Biochemistry I/ZAFES, Goethe-University Frankfurt, Theodor-Stern-Kai 7, Frankfurt, Germany.
authors: M
authors: M
authors: Jung
authors: Institute of Biochemistry I/ZAFES, Goethe-University Frankfurt, Theodor-Stern-Kai 7, Frankfurt, Germany.
authors: B
authors: B
authors: Brüne
authors: Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona, Spanish Research Council (IIBB-CSIC, IDIBAPS), Barcelona, Spain.
authors: F
authors: F
authors: Pi
authors: Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona, Spanish Research Council (IIBB-CSIC, IDIBAPS), Barcelona, Spain.
authors: C
authors: C
authors: Mastora
authors: 1] Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona, Spanish Research Council (IIBB-CSIC, IDIBAPS), Barcelona, Spain [2] CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Department of Experimental Pathology, IIBB-CSIC-IDIBAPS, Barcelona, Spain.
authors: G
authors: G
authors: Hotter
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000201:enzymology*; D050156:Adipogenesis; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D053538:Keratin-18 / Q000235:genetics / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology
chemical_list: D053538:Keratin-18; D020780:Matrix Metalloproteinase 9