Exosomal miRNA-26b-5p from PRP suppresses NETs by targeting MMP-8 to promote diabetic wound healing

作者全名："Rui, Shunli; Dai, Linrui; Zhang, Xiaoshi; He, Min; Xu, Fan; Wu, Wei; Armstrong, David G.; You, Yuehua; Xiao, Xiaoqiu; Ma, Yu; Chen, Yan; Deng, Wuquan"

作者地址："[Rui, Shunli; Dai, Linrui; Zhang, Xiaoshi; He, Min; Xu, Fan; Ma, Yu; Chen, Yan; Deng, Wuquan] Chongqing Univ, Chongqing Emergency Med Ctr, Sch Med, Dept Endocrinol & Metab,Cent Hosp, Chongqing 400014, Peoples R China; [Wu, Wei] Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing 400044, Peoples R China; [Armstrong, David G.] Univ Southern Calif, Dept Surg, Keck Sch Med, Los Angeles, CA 90033 USA; [You, Yuehua; Xiao, Xiaoqiu] Chongqing Med Univ, Chongqing Key Lab Translat Med Major Metab Dis, Affiliated Hosp 1, Chongqing 400010, Peoples R China"

通信作者："Ma, Y; Chen, Y; Deng, WQ (通讯作者)，Chongqing Univ, Chongqing Emergency Med Ctr, Sch Med, Dept Endocrinol & Metab,Cent Hosp, Chongqing 400014, Peoples R China."

来源：JOURNAL OF CONTROLLED RELEASE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001326039700001

JCR分区：Q1

影响因子：10.8

年份：2024

卷号：372

期号：　

开始页：221

结束页：233

文献类型：Article

关键词：PRP-exos; miRNA-26b-5p; Diabetic wound healing; NETs; MMP-8

摘要："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 MMP8. These findings provide valuable insights for developing novel therapeutic strategies to enhance wound healing in individuals suffering from DFUs."

基金机构："National Natural Science Foundation of China [82370903]; Natural Science Foundation of Chongqing Municipal Science and Technology Bureau [CSTB2022NSCQ-MSX0489, cstc2021jcyj-msxmX1091]; Fund of Sichuan Provincial Western Psychiatric Association's CSPC LEADING Scientific Research Project [WL2021002]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (Grant No. 82370903) , the Natural Science Foundation of Chongqing Municipal Science and Technology Bureau (Grant No. CSTB2022NSCQ-MSX0489 and Grant No. cstc2021jcyj-msxmX1091) , and the fund of Sichuan Provincial Western Psychiatric Association's CSPC LEADING Scientific Research Project (Grant No. WL2021002) ."