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 and 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.

中文翻译：

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来自 PRP 的外泌体 miRNA-26b-5p 通过靶向 MMP-8 抑制 NET，促进糖尿病伤口愈合


利用富含血小板的血浆（PRP）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陷阱 (NET) 的潜在影响。本研究旨在调查糖尿病环境对 PRP-Exos 的影响、它们与中性粒细胞的通讯，以及随后对 NET 和伤口愈合的影响。通过bulk-seq和Western blotting，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 之间的通讯中发挥着重要作用。在我们的实验中，我们发现 PRP-Exos miR-26b-5p 通过抑制 NET 有效改善糖尿病伤口愈合。进一步的测试验证了 miR-26b-5p 通过靶向 MMP-8 对 NETs 的抑制作用。两项实验均表明，来自 PRP-Exos 的 miRNA-26b-5p 通过靶向 MMP-8 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 之间通讯中的重要性，通过靶向 MMP-8 来破坏糖尿病伤口中 NET 的形成。这些发现为开发新的治疗策略以增强 DFU 患者的伤口愈合提供了宝贵的见解。