Sphingosine-1-phosphate derived from PRP-Exos promotes angiogenesis in diabetic wound healing via the S1PR1/AKT/FN1 signalling pathway

作     者：Tianyi Chen Peiyang Song Min He Shunli Rui Xiaodong Duan Yu Ma David G.Armstrong Wuquan Deng 

作者机构：Department of EndocrinologyChongqing Emergency Medical CenterChongqing University Central HospitalSchool of MedicineChongqing UniversityChongqing400014China Department of RehabilitationThe Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan646000China Department of SurgeryKeck School of Medicine of University of Southern CaliforniaLos AngelesCA 90033USA 

出 版 物：《Burns & Trauma》 (烧伤与创伤（英文）)

年 卷 期：2023年第11卷第1期

页      面：229-244页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the Chongqing Youth High-end Talent Studio(Grant No.ZQNYXGDRCGZS2021008) the fund of Sichuan Provincial Western Psychiatric Association’s CSPC LEADING Scientific Research Project(Grant No.WL2021002) the Natural Science Foundation of Chongqing Municipal Science and Technology Bureau(CSTB2022NSCQ-MSX0489) partially supported by National Institutes of Health,National Institute of Diabetes and Digestive and Kidney Diseases Award Number 1R01124789-01A1 National Science Foundation(NSF)Center to Stream Healthcare in Place(#C2SHiP)CNS Award Number 2052578 awarded to DGA 

主　　题：Exosomes Platelet-rich plasma Diabetic foot ulcer Wound healing Sphingosine-1-phosphate 

摘      要：Background:Sphingosine-1-phosphate(S1P),a key regulator of vascular homeostasis and angiogenesis,is enriched in exosomes derived from platelet-rich plasma(PRP-Exos).However,the potential role of PRP-Exos-S1P in diabetic wound healing remains *** this study,we investigated the underlying mechanism of PRP-Exos-S1P in diabetic angiogenesis and wound ***:Exosomes were isolated from PRP by ultracentrifugation and analysed by transmission electron microscopy,nanoparticle tracking analysis and western *** concentration of S1P derived from PRP-Exos was measured by enzyme-linked immunosorbent *** expression level of S1P receptor1–3(S1PR1–3)in diabetic skin was analysed by *** analysis and proteomic sequencing were conducted to explore the possible signalling pathway mediated by PRP-Exos-S1P.A diabetic mouse model was used to evaluate the effect of PRP-Exos on wound *** for cluster of differentiation 31(CD31)was used to assess angiogenesis in a diabetic wound ***:In vitro,PRP-Exos significantly promoted cell proliferation,migration and tube ***,PRP-Exos accelerated the process of diabetic angiogenesis and wound closure in vivo.S1P derived from PRP-Exos was present at a high level,and S1PR1 expression was significantly elevated compared with S1PR2 and S1PR3 in the skin of diabetic patients and ***,cell migration and tube formation were not promoted by PRP-Exos-S1P in human umbilical vein endothelial cells treated with *** the diabetic mouse model,inhibition of S1PR1 expression at wounding sites decreased the formation of new blood vessels and delayed the process of wound *** analysis and proteomics indicated that fibronectin 1(FN1)was closely related to S1PR1 due to its colocalization in the endothelial cells of human *** study supported that FN1 plays an important role in the PRP-Exos-S1Pmediated S1PR1/protein kinase B signalling