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). 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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Author:Marina Ventayol, Jose Luis Viñas, Anna Sola, Michaela JungORCiD, Bernhard BrüneORCiD, Felip Pi, Chrysoula Mastora, Georgina Hotter
URN:urn:nbn:de:hebis:30:3-329864
DOI:https://doi.org/10.1038/cddis.2014.2
ISSN:2041-4889
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24503540
Parent Title (English):Cell death & disease
Publisher:Nature Publishing Group
Place of publication:London [u. a.]
Document Type:Article
Language:English
Date of Publication (online):2014/02/11
Date of first Publication:2014/02/06
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/02/11
Tag:MMP9; adipose-derived stem cells (ASCs); differentiation; miRNA let-7e
Volume:5
Issue:e1048
Page Number:10
First Page:1
Last Page:10
Note:
Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
HeBIS-PPN:364051809
Institutes:Medizin / Medizin
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0