title: Inhibitory effect of hsa-miR-590-5p on cardiosphere-derived stem cells differentiation through downregulation of TGFB signaling.
abstract: The cardiac cells generation via stem cells differentiation is a promising approach to restore the myocardial infarction. Promoted by our primary bioinformatics analysis as well as some previously published data on potential role of hsa-miR-590-3p in cardiogenesis, we have tried to decipher the role of miR-590-5p during the course of differentiation of cardiosphere-derived cells (CDCs). The differentiation induction of CDCs by TGFB1 was confirmed by real-time PCR, ICC, and flow cytometry. The expression pattern of hsa-miR-590-5p and some related genes were examined during the differentiation process. In order to study the role of miR-590-5p in cardiac differentiation, the effect of miR-590 overexpression in CDCs was studied. Evaluating the expression patterns of miR-590 and its potential targets (TGFBRs) during the course of differentiation, demonstrated a significant downregulation of miR-590 and an upregulation of TGFBR2, following the treatment of CDCs with TGFB1. Therefore, we proposed a model in which TGFB1 exerts its differentiation induction via downregulation of miR-590, and hence the higher transcriptional expression level of TGFBR2. In accordance with our proposed model, transfection of CDCs by a pLenti-III-hsa-mir-590-GFP expression vector before or after the first TGFB1 treatment caused a significant alteration in the expression levels of TGFBRs. Moreover, our data revealed that overexpression of miR-590 before TGFB1 induction was able to attenuate the CDCs differentiation probably via the reduction of TGFBR2 expression level. Altogether, our data suggest an inhibitory role of miR-590 during the cardiac differentiation of CDCs which its suppression might elevate the rate of differentiation.
authors.affiliation: Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Ekhteraei-Tousi
authors.forename: Bahram
authors.initials: B
authors.lastname: Mohammad-Soltani
authors.forename: Majid
authors.initials: M
authors.lastname: Sadeghizadeh
authors.forename: Seyed Javad
authors.initials: SJ
authors.lastname: Mowla
authors.forename: Sepideh
authors.initials: S
authors.lastname: Parsi
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C568221:MIRN590 microRNA, human; D035683:MicroRNAs; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: CARDIOSPHERE-DERIVED STEM CELLS; DIFFERENTIATION; TGFB1; TGFBR2; hsa-miR-590-5p