Downregulation of MiR-199b-5p Inducing Differentiation of Bone-Marrow Mesenchymal Stem Cells (BMSCs) Toward Cardiomyocyte-Like Cells via HSF1/HSP70 Pathway

Abstract

BackgroundBone-marrow mesenchymal stem cells (BMSCs) are pluripotent stem cells with potent self-renewal and differentiation ability that are widely used in transplantation of cell therapy. But the mechanism on microRNA (miRNA) regulating stem cell differentiation is complicated and unclear. The aim of this study was to investigate whether miR-199b-5p is involved in differentiation of cardiomyocyte-like cells and identify potential signal pathways in BMSCs.Material/MethodsMouse BMSCs were treated with 5-azacytidine and transfected by miR-199b-5p mimic and inhibitor, respectively. qRT-PCR was used to detect the expression of miR-199b-5p in BMSCs, 5-azacytidine treated BMSCs, and neonatal murine cardiomyocytes. The expression of cardiac specific genes and the HSF1/HSP70 signal pathway were examined by qRT-PCR or western blotting. The proliferation and migration of BMSCs were evaluated by CCK-8 assay and wound-healing assay.ResultsThe expression of miR-199b-5p decreased gradually in the process of differentiation of BMSCs toward cardiomyocyte-like cells. The expression of cardiac specific genes and HSF1/HSP70 were increased in the miR-199b-5p inhibitor group; however, the miR-199b-5p mimic group presented an opposite result. Both the miR-199b-5p inhibitor group and the miR-199b-5p mimic group had no influence on BMSCs proliferation and migration. Using lentivirus vectors bearing HSF1 shRNA to silence HSF1 and HSP70, the anticipated elevated expression effect of cardiac specific genes induced by miR-199b-5p inhibitor was suppressed.ConclusionsDownregulation of miR-199b-5p induced differentiation of BMSCs toward cardiomyocyte-like cells partly via the HSF1/HSP70 signaling pathway, and had no influence on BMSCs proliferation and migration.

miR‑144 promotes the proliferation and differentiation of bone mesenchymal stem cells by downregulating the expression of SFRP1

“…In recent years, miRNAs have been shown to be involved in the occurrence, development and prognosis of various diseases, and have also been used to diagnose and treat diseases (17,18). miRNAs also regulate the differentiation of mesenchymal stem cells and osteoblasts (19,20). During the processes of bone differentiation and regeneration, abnormal miRNA expression is closely associated with OP (21,22).…”

CDR1as related miRNA-mRNA networks in differentiating goat skeletal muscle satellite cells

“…miR-146a-5p has been demonstrated to signi cantly induced VSMC proliferation [55], however, lack of miR-146a did not increase muscular dystrophy in mdx mice but was highly expressed in dystrophic muscle [79]. Decreased in the expression of miR-199b-5p induces differentiation of Bone-Marrow Mesenchymal Stem Cells (BMSCs) toward Cardiomyocyte-Like Cells [51]. The Knockdown of miR-199a-3p inhibits slow-to-fast muscle ber type change in mice and C2C12 Cells [80].…”

miR‐199b‐5p promoted chondrogenic differentiation of C3H10T1/2 cells by regulating JAG1

“…Furthermore, notch signaling pathway has a known effect on cell differentiation via miRNAs. In previous studies, miR-199b-5p has been shown to be related with notch signaling pathway in various cell types including cancer (Chen et al, 2019;Dai et al, 2018;Won et al, 2013;Wu, Chen, Liu, Lai, & Liu, 2018;Zhao et al, 2016). Moreover, has also been involved in the certain pathologies process such as in ovarian cancer (Liu et al, 2014), medulloblastoma (Andolfo et al, 2012;Garzia et al, 2009), myocardial infarction (Duygu et al, 2017), and vascular pathologies (Briot et al, 2014).…”