miRNA let-7e Modulates the Wnt Pathway and Early Nephrogenic Markers in Mouse Embryonic Stem Cell Differentiation |
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| Authors: | Jose Luis Vi?as Marina Ventayol Bernhard Brüne Michaela Jung Anna Sola Felip Pi Chrysoula Mastora Georgina Hotter |
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| Institution: | 1. Departament of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC, IDIBAPS), Barcelona, Spain.; 2. CIBER-BBN, Networking Center on Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain.; 3. Departamento de Fisiología, Universidad de Barcelona, Barcelona, Spain.; 4. Institute of Biochemistry I/ZAFES, Goethe-University Frankfurt, Theodor-Stern-Kai, Frankfurt, Germany.; University of Ulm, Germany, |
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| Abstract: | This study indicates that embryonic stem cells ESCs] cultured with retinoic acid and activin A significantly upregulate the miRNA let-7e. This specific miRNA modulates the Wnt pathway and the expression of early nephrogenic markers under these differentiation conditions. The differentiation markers WT1, Pax2 and Wnt4 were downregulated when miRNA let-7e was silenced, thus indicating the role of miRNA let-7e in the differentiation process. PKCβ, GSK3β phosphorylation (GSK3βP) and β-catenin expression was reduced in differentiated cells and reversed by miRNA let-7e silencing. Addition of a PKCβ inhibitor to the miRNA let-7e silenced cells abolished let-7e-derived effects in differentiation markers, and reversed the increase in GSK3βP and β-catenin, thus indicating that miRNA let-7e is involved in differentiation via the modulation of GSK3β phosphorylation and β-catenin production. |
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