MALAT1 participates in the role of platelet-rich plasma exosomes in promoting wound healing of diabetic foot ulcer

Abstract

Exosomes isolated from platelet-rich plasma (PRP-exos) have been recently deemed as an optimized therapeutic strategy in diabetic foot ulcer (DFU) treatment. Herein, we aimed to explore whether MALAT1 participates in DFU wound healing by PRP-exos treatment and the related preliminary mechanism. Fibroblasts were isolated from healthy donors and DFU patients, and the expression of MALAT1, miR-374a-3p and DNMT3A were detected by RT-PCR. The effect of MALAT1 and miR-374a-3p on DFU fibroblast function was verified by gain/loss of function experiment. The targeted binding of MALAT and miRNA was verified by double luciferase reporter gene assay. PRP-exos were isolated from normal human blood and characterized, and then co-cultured with DFU fibroblasts. The MALAT1 expression was donwregulated while the miR-374a-5p expression was upregulated in DFU fibroblasts. Double luciferase reporter gene assay demonstrated the targeted binding of MALAT and miR-374a-5p. Overexpression of MALAT1 or knockdown of miR-374a-5p could increase viability and inhibit apoptosis and pyroptosis of DFU fibroblast. And overexpression of miR-374a-5p reversed the effect of PRR-exos or MALAT1 overexpression on cell viability, apoptosis and pyroptosis. Collectively, MALAT1 mediated signal axis participates in the role of PRP-exos in promoting DFU wound healing, which may help identify optimal targets and effective therapies for DFU treatment.