Abstract：
The utilization of platelet-rich plasma (PRP) has exhibited potential as a therapeutic approach for the management of diabetic foot ulcers (DFUs). However, it is currently not well understood how the diabetic environment may influence PRP-derived exosomes (PRP-Exos) and their potential impact on neutrophil extracellular traps (NETs). This study aims to investigate the effects of the diabetic environment on PRP-Exos, their communication with neutrophils, and the subsequent influence on NETs and wound healing. Through bulk-seq and Western blotting, we confirmed the increased expression of MMP-8 in DFUs. Additionally, we discovered that miRNA-26b-5p plays a significant role in the communication between DFUs and PRP-Exos. In our experiments, we found that PRP-Exos miR-26b-5p effectively improved diabetic wound healing by inhibiting NETs. Further tests validated the inhibitory effect of miR-26b-5p on NETs by targeting MMP-8. Both in vitro and in vivo experiments showed that miRNA-26b-5p from PRP-Exos promoted wound healing by reducing neutrophil infiltration through its targeting of MMP-8. This study establishes the importance of miR-26b-5p in the communication between DFUs and PRP-Exos, disrupting NETs formation in diabetic wounds by targeting MMP-8. These findings provide valuable insights for developing novel therapeutic strategies to enhance wound healing in individuals suffering from DFUs.
摘要：
富血小板血浆（PRP）的利用已显示出作为治疗糖尿病足溃疡（DFU）的治疗方法的潜力。然而,目前尚不清楚糖尿病环境如何影响PRP衍生的外泌体(PRP-Exos)及其对中性粒细胞胞外诱捕网(NETs)的潜在影响.本研究旨在探讨糖尿病环境对PRP-Exos,它们与嗜中性粒细胞的交流，以及随后对NETs和伤口愈合的影响。通过bulk-seq和Western印迹,我们证实了DFU中MMP-8的表达增加。此外,我们发现miRNA-26b-5p在DFU和PRP-Exos之间的通讯中起着重要作用。在我们的实验中,我们发现PRP-ExosmiR-26b-5p通过抑制NETs有效改善糖尿病伤口愈合.进一步的试验验证了miR-26b-5p通过靶向MMP-8对NETs的抑制作用。体外和体内实验均表明，来自PRP-Exos的miRNA-26b-5p通过靶向MMP-8来减少中性粒细胞浸润，从而促进伤口愈合。这项研究确立了miR-26b-5p在DFU和PRP-Exos之间的通信中的重要性。通过靶向MMP-8破坏糖尿病伤口中的NETs形成。这些发现为开发新的治疗策略以增强患有DFU的个体的伤口愈合提供了有价值的见解。
