NF‑κB‑miR15a‑bFGF/VEGFA axis contributes to the impaired angiogenic capacity of BM‑MSCs in high fat diet‑fed mice.

Abstract

Potent paracrine properties, such as secretion of angiogenic cytokines and growth factors, have been considered essential for the function of mesenchymal stem cells (MSCs) in tissue regeneration and repair. The present study determined that bone marrow‑derived mesenchymal stem cells from mice fed a high fat diet (HFD) had reduced pro‑angiogenic capacity, as evident from the reduced expression of vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor (bFGF); therefore, a reduced number of branches was induced in the angiogenesis assay. Additionally, the present study determined that miR‑15a, a putative microRNA targeting both VEGFA and bFGF, may simultaneously downregulate bFGF and VEGFA expression levels through the 3'‑untranslated region. Inhibition of miR‑15a using an antagonist restored the expression of VEGFA and bFGF under fatty acid treatment and thus the angiogenic capacity. Furthermore, the HFD and fatty acids treatments transcriptionally activated the expression of miR‑15a via nuclear factor‑κB. In conclusion, the findings of the present study revealed that inhibition of miR‑15a may restore the therapeutic efficacy of mesenchymal stem cells in patients suffering from obesity.