Endothelial progenitor cell (EPCs)-derived exosomal miR-30d-5p inhibits the inflammatory response of high glucose-impaired fibroblasts by affecting the M1/M2 polarization of macrophages

Abstract

Abstract Background: Diabetes is a common chronic disease which has caused a great burden on families and society. The treatment of diabetes has always been a hotspot. This study aimed to explore the effect and mechanism of miR-30d-5pon inflammation of high glucose-impaired human keloid fibroblasts (HKF). Methods: Differently-expressed miRNAs were predicted by bioinformatics methods. Exosomes were observed by transmission electron microscope. Exosome particle sizes were measured by NanoSight. Western Blot was used to detect the expression of CD81, CD63, CD9, and Calnexin. QRT-PCR was used to detect the expression of miR-30d-5p, IL-1β, TNF-α, VEGF, FGF21, NRF2, and HO-1. The levels of IL-1β, TNF-α, IL-6, IL-10, and TGF-β were determined by ELISA. Cell apoptosis and CD86, CD206 positive cells were detected by flow cytometry. Results: Tori formula could promote the secretion of endothelial progenitor cell (EPCs) exosomes. EPCs exosomes and miR-30d-5p could stimulate the proliferation of HKF impaired by high glucose and the expression of IL-10 and TGF-β. MiR-30d-5p inhibited the proliferation of M1 macrophages and the expression of IL-1β and TNF-α. It could also promote the proliferation of M2 macrophages and the expression of CCL17 and CCL22. Moreover, miR-30d-5p stimulated the expression of VEGF, FGF21, NRF2, and HO-1, as well as suppressed the expression of IL-1β, TNF-α, and IL-6. MiR-30d-5p also restrained the apoptosis of impaired HKF. Conclusion: This study confirmed that miR-30d-5p could promote the M1/M2 polarization and inhibit the inflammatory response of impaired HKF, which provided a certain idea and direction for treating diabetes.