The cardiac stem cells (CSCs) are essential in improving myocardial infarction (MI). Although miR-199a-5p and hypoxia-inducible factor-1 alpha (HIF-1α) were proven to participate in the process of heart repair, the related mechanisms are still unclear. This study aimed to explore the effects of miR-199a-5p and HIF-1α on c-kit+ cells and their regulatory mechanisms. After isolating, purifying, and identifying CSCs (c-kit+ cells) from mice, they were subjected to a hypoxia model. After the c-kit+ cells were transfected with corresponding transfectants, the CCK-8, EdU staining, and wound healing approaches were used to evaluate their cell viability, proliferation, and migration. The targeted relation between miR-199a-5p and HIF-1α was determined using a dual-luciferase reporter. Immunofluorescence staining, RT-qPCR, and Western blot approaches were employed to determine Nkx2.5, CD31, α-SMA, miR-199a-5p, and HIF-1α expression. Overexpressing miR-199a-5p and knocking down HIF-1α both inhibited the cell viability (p<0.01), reduced the proliferation (p<0.05), suppressed the migration (p<0.001), and down-regulated the Nkx2.5, CD31, and α-SMA expression of c-kit+ cells (p<0.05). Overexpressing HIF-1α effectively reversed the effects of overexpressing miR-199a-5p on c-kit+ cells (p<0.05). Taken together, miR-199a-5p negatively targeted HIF-1α to inhibit the proliferation, migration, and differentiation of c-kit+ cells.
Li et al. (Mon,) studied this question.