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.

Retracted: microRNA‐590‐5p targets transforming growth factor β1 to promote chondrocyte apoptosis and autophagy in response to mechanical pressure injury

“…26 A work of Gajewska et al 27 has revealed that TGFβ1 can induce apoptosis and autophagy in bovine mammary epithelial UV1 cells. 30 In our study, miR-590-5p could negatively regulate the protein expression levels of TGFβ1. 28 In addition, miR-455 can regulate TGFβ signaling, thus contributing to cartilage destruction in osteoarthritis.…”

MiR‐590 Promotes Transdifferentiation of Porcine and Human Fibroblasts Toward a Cardiomyocyte‐Like Fate by Directly Repressing Specificity Protein 1

“…30,31 miR-590 regulates signaling pathways (TGF-b, protein kinase B) involved in cardiac fibrosis/remodeling, embryonic stem cell proliferation/cardiac differentiation, and metabolism by suppressing TGF-b receptor II. [32][33][34][35] Interestingly, whereas overexpression of miR-590 has been shown to be associated with cardiac regeneration, improved cardiac function and reduced scarring following MI, 22 miR-590 downregulation was correlated with atrial fibrosis and atrial fibrillation. 35 Taken together, these data clearly support a role for miR-590 in cardiac physiology and disease.…”

TrkC‐miR2 regulates TGFβ signaling pathway through targeting of SMAD3 transcript

“…Although it has been shown that SMAD3 gene is downregulated after TrkC ‐ miR2 overexpression (Figure ), downregulation of SMAD7 suggests that the whole TGFβ signaling pathway is also downregulated (Figure ). However, the c‐MYC expression alteration was not significant, which could be justified by its involvement in other pathways such as the Wnt Pathway …”

“…The TGFβ signaling pathway plays a pivotal role in cardiac differentiation . TrkC as one of the members of the neurotrophin pathway is also known to be involved in the formation and functioning of heart and myocardial vasculature .…”