Sphingosine-1-phosphate derived from PRP-Exos promotes angiogenesis in diabetic wound healing via the S1PR1/AKT/FN1 signalling pathway.
Sphingosine-1-phosphate derived from PRP-Exos promotes angiogenesis in diabetic wound healing via the S1PR1/AKT/FN1 signalling pathway.
复制标题
源自富血小板血浆外泌体（PRP-Exos）的1-磷酸鞘氨醇通过S1PR1/AKT/FN1信号通路促进糖尿病伤口愈合过程中的血管生成。
DOI：
10.1093/burnst/tkad003
复制
发表时间：
2023
期刊：
影响因子：
5.3
通讯作者：
Deng, Wuquan
中科院分区：
文献类型：
--
作者：
Chen, Tianyi;Song, Peiyang;He, Min;Rui, Shunli;Duan, Xiaodong;Ma, Yu;Armstrong, David G.;Deng, Wuquan
鞘氨醇-1-磷酸（S1 P）是血管稳态和血管生成的关键调节剂，富含于来源于富血小板血浆（PRP-Exos）的外泌体中。然而，PRP-Exos-S1 P在糖尿病伤口愈合中的潜在作用仍不清楚。在这项研究中，我们研究了PRP-Exos-S1 P在糖尿病血管生成和伤口修复中的潜在机制。通过超离心从PRP中分离外来体，并通过透射电子显微镜、纳米颗粒跟踪分析和蛋白质印迹法进行分析。通过酶联免疫吸附测定法测量来自PRP-Exos的S1 P的浓度。Q-PCR检测糖尿病皮肤中S1 P受体1 -3（S1 PR 1 -3）的表达水平。通过生物信息学分析和蛋白质组测序，探讨PRP-Exos-S1 P可能的信号转导途径。使用糖尿病小鼠模型来评估PRP-Exos对伤口愈合的影响。使用分化簇31（CD 31）的免疫荧光来评估糖尿病伤口模型中的血管生成。 在体外，PRP-Exos显著促进细胞增殖、迁移和管形成。此外，PRP-Exos加速了体内糖尿病血管生成和伤口闭合的过程。在糖尿病患者和动物的皮肤中，源自PRP-Exos的S1 P以高水平存在，并且与S1 PR 2和S1 PR 3相比，S1 PR 1表达显著升高。然而，在用shS 1 PR 1处理的人脐静脉内皮细胞中，PRP-Exos-S1 P并不促进细胞迁移和管形成。在糖尿病小鼠模型中，抑制S1 PR 1在伤口部位的表达减少了新血管的形成，并延迟了伤口闭合的过程。生物信息学分析和蛋白质组学研究表明，FN 1与S1 PR 1在人皮肤内皮细胞中存在共定位，二者关系密切。进一步的研究支持FN 1在PRP-Exos-S1 P介导的S1 PR 1/蛋白激酶B信号通路中发挥重要作用。PRP-Exos-S1 P通过S1 PR 1/蛋白激酶B/FN 1信号通路促进糖尿病伤口愈合中的血管生成。我们的研究结果为将来使用PRP-Exos治疗糖尿病足溃疡提供了初步的理论基础。
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 unclear. In this study, we investigated the underlying mechanism of PRP-Exos-S1P in diabetic angiogenesis and wound repair. Exosomes were isolated from PRP by ultracentrifugation and analysed by transmission electron microscopy, nanoparticle tracking analysis and western blotting. The concentration of S1P derived from PRP-Exos was measured by enzyme-linked immunosorbent assay. The expression level of S1P receptor1–3 (S1PR1–3) in diabetic skin was analysed by Q-PCR. Bioinformatics 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 healing. Immunofluorescence for cluster of differentiation 31 (CD31) was used to assess angiogenesis in a diabetic wound model. In vitro, PRP-Exos significantly promoted cell proliferation, migration and tube formation. Furthermore, 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 animals. However, cell migration and tube formation were not promoted by PRP-Exos-S1P in human umbilical vein endothelial cells treated with shS1PR1. In the diabetic mouse model, inhibition of S1PR1 expression at wounding sites decreased the formation of new blood vessels and delayed the process of wound closure. Bioinformatics analysis and proteomics indicated that fibronectin 1 (FN1) was closely related to S1PR1 due to its colocalization in the endothelial cells of human skin. Further study supported that FN1 plays an important role in the PRP-Exos-S1P-mediated S1PR1/protein kinase B signalling pathway. PRP-Exos-S1P promotes angiogenesis in diabetic wound healing via the S1PR1/protein kinase B/FN1 signalling pathway. Our findings provide a preliminary theoretical foundation for the treatment of diabetic foot ulcers using PRP-Exos in the future.
登录
查看更多内容
影响因子：
10.8
作者：
Heller, Regine;Chang, Qing;Wetzker, Reinhard
通讯作者：
Wetzker, Reinhard
影响因子：
5.2
作者：
Everett E;Mathioudakis N
通讯作者：
Mathioudakis N
影响因子：
4.6
作者：
Kase Y;Uzawa K;Wagai S;Yoshimura S;Yamamoto JI;Toeda Y;Okubo M;Eizuka K;Ando T;Nobuchi T;Kawasaki K;Saito T;Iyoda M;Nakashima D;Kasamatsu A;Tanzawa H
通讯作者：
Tanzawa H
影响因子：
20.3
作者：
McVey, Mark J;Weidenfeld, Sarah;Kuebler, Wolfgang M
通讯作者：
Kuebler, Wolfgang M
影响因子：
12.4
作者：
Liang Y;Duan L;Lu J;Xia J
通讯作者：
Xia J