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Volume 41 Issue 3
Mar.  2025
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2025  >  41(3): 258-267
Feng JY,Fei X,Fang SYH,et al.Influence and mechanism of extracellular vesicles derived from human adipose-derived mesenchymal stem cells on pyroptosis of human umbilical vein endothelial cells induced by high glucose[J].Chin J Burns Wounds,2025,41(3):258-267.DOI: 10.3760/cma.j.cn501225-20240120-00025.
Citation: Feng JY,Fei X,Fang SYH,et al.Influence and mechanism of extracellular vesicles derived from human adipose-derived mesenchymal stem cells on pyroptosis of human umbilical vein endothelial cells induced by high glucose[J].Chin J Burns Wounds,2025,41(3):258-267.DOI: 10.3760/cma.j.cn501225-20240120-00025.
shu

Influence and mechanism of extracellular vesicles derived from human adipose-derived mesenchymal stem cells on pyroptosis of human umbilical vein endothelial cells induced by high glucose

doi: 10.3760/cma.j.cn501225-20240120-00025
  • 1.

    Medical Center of Burn Plastic and Wound Repair, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China

  • 2.

    Medical College of Nanchang University, Nanchang 330006, China

Funds:

Regional Science Foundation Project of National Natural Science Foundation of China 82460447, 81460293

Chongqing Traditional Chinese Medicine Inheritance and Innovation Team Project 2023090006KJZX2022WJW008

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  • Corresponding author: Liu Dewu, Email: dewuliu@126.com
  • Received Date: 2024-01-20
    Abstract
  •   Objective  To investigate the influence and mechanism of extracellular vesicles (EVs) derived from human adipose-derived mesenchymal stem cells (hADMSCs), i.e. hADMSC-EVs on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by high glucose, with the aim of providing evidence for improving vascular function in diabetic wounds.  Methods  This study was an experimental research. The umbilical cords from 5 women aged 25 to 40 years were collected who had normal vaginal delivery at the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Nanchang University from June to September in 2023, and HUVECs were isolated and successfully identified. Adipose tissue was obtained from 6 healthy women aged 25 to 35 years who underwent abdomen liposuction at the Department of Plastic Surgery of the above-mentioned hospital in the same period. After hADMSCs were isolated, hADMSC-EVs were extracted and successfully identified. The fourth passage of HUVECs were cultured in endothelial cell medium containing glucose in a molarity of 33 mmol/L and divided into phosphate buffered solution (PBS) group cultured with PBS, EV group cultured with hADMSC-EVs, and EV+LY294002 group cultured with hADMSC-EVs and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway inhibitor LY294002. Western blotting was used to detect the expressions of PI3K/Akt signaling pathway-related proteins PI3K and Akt, and pyroptosis-related proteins nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific protease-1 (caspase-1), gasdermin D, interleukin-1β (IL-1β), and IL-18 of cells after 48 hours of culture. A cell counting kit-8 was used to test the proliferation levels of cells at 0 (immediately), 12, 24, 36, 48, 60, and 72 hours of culture. After 48 hours of culture, the cell scratch test was performed and the cell migration rates at 12 and 24 hours after scratching were calculated; the cell Transwell assay was conducted and the number of cells migrating in 24 hours was calculated; the cell tube formation experiment was performed, and the total length of tube formation and the number of branch nodes were measured and counted. The sample size was 3.  Results  After 48 hours of culture, the protein expressions of PI3K and Akt of cells in EV group were significantly higher than those in PBS group (P<0.05), and the protein expressions of PI3K and Akt of cells in EV+LY294002 group were significantly lower than those in EV group (P<0.05). After 48 hours of culture, the protein expressions of NLRP3, caspase-1, gasdermin D, IL-1β, and IL-18 of cells in EV group were 0.54±0.08, 0.96±0.11, 0.525±0.061, 1.216±0.039, and 1.317±0.023, respectively, which were significantly lower than 2.32±0.11, 1.86±0.07, 1.256±0.113, 2.589±0.084, and 2.042±0.132 in PBS group (P<0.05); the protein expressions of NLRP3, caspase-1, gasdermin D, IL-1β, and IL-18 of cells in EV+LY294002 group were 1.16±0.05, 1.37±0.06, 0.962±0.028, 1.834±0.017, and 1.803±0.065, respectively, which were significantly higher than those in EV group (P<0.05). At 12, 24, 36, 48, 60, and 72 hours of culture, the proliferation levels of cells in EV group were significantly higher than those in PBS group (P<0.05), and the proliferation levels of cells in EV+LY294002 group were significantly lower than those in EV group (P<0.05). After 48 hours of culture, the cell migration rates at 12 and 24 hours after scratching in EV group were significantly higher than those in PBS group (P<0.05), and the cell migration rates at 12 and 24 hours after scratching in EV+LY294002 group were significantly lower than those in EV group (P<0.05); the number of cells migrating in 24 hours in EV group was significantly greater than that in PBS group (P<0.05), and the number of cells migrating in 24 hours in EV+LY294002 group was significantly less than that in EV group (P<0.05). After 48 hours of culture, compared with those in PBS group, the total length of tube formation of cells in EV group was significantly prolonged (P<0.05), and the number of branch nodes was significantly increased (P<0.05); compared with those in EV group, the total length of tube formation in EV+LY294002 group was significantly shortened (P<0.05), and the number of branch nodes was significantly decreased (P<0.05).  Conclusions  hADMSC-EVs can inhibit the expression of pyroptosis-related proteins in HUVECs induced by high glucose through the PI3K/Akt signaling pathway and improve the proliferation, migration, and angiogenesis capabilities of HUVECs.

     

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    • References(40)
  • [1]
    PatelS,SrivastavaS,SinghMR,et al.Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing[J].Biomed Pharmacother,2019,112:108615.DOI: 10.1016/j.biopha.2019.108615.
    [2]
    PopMA,AlmquistBD.Biomaterials: a potential pathway to healing chronic wounds?[J].Exp Dermatol,2017,26(9):760-763.DOI: 10.1111/exd.13290.
    [3]
    ZhouC,ZhangB,YangY,et al.Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing[J].Stem Cell Res Ther,2023,14(1):107.DOI: 10.1186/s13287-023-03345-0.
    [4]
    陈祎琦,周莹芊,魏茜,等.负载人脐带间充质干细胞来源的小细胞外囊泡的甲基丙烯酸酐化明胶水凝胶治疗小鼠全层皮肤缺损创面的效果[J].中华烧伤与创面修复杂志,2024,40(4):323-332.DOI: 10.3760/cma.j.cn501225-20231218-00248.
    [5]
    居裔昆,方柏荣.脂肪间充质干细胞外囊泡促进创面血管生成机制的研究进展[J].中华烧伤与创面修复杂志,2023,39(1):85-90.DOI: 10.3760/cma.j.cn501225-20220322-00080.
    [6]
    LelekJ,Zuba-SurmaEK.Perspectives for future use of extracellular vesicles from umbilical cord- and adipose tissue-derived mesenchymal stem/stromal cells in regenerative therapies-synthetic review[J].Int J Mol Sci,2020,21(3):799.DOI: 10.3390/ijms21030799.
    [7]
    BergsbakenT,FinkSL,CooksonBT.Pyroptosis: host cell death and inflammation[J].Nat Rev Microbiol,2009,7(2):99-109.DOI: 10.1038/nrmicro2070.
    [8]
    MullaJ,KattiR,ScottMJ.The role of gasdermin-D-mediated pyroptosis in organ injury and its therapeutic implications[J].Organogenesis,2023,19(1):2177484.DOI: 10.1080/15476278.2023.2177484.
    [9]
    BandharamN,LockeyRF,KolliputiN.Pyroptosis inhibition in disease treatment: opportunities and challenges[J].Cell Biochem Biophys,2023,81(4):615-619.DOI: 10.1007/s12013-023-01181-w.
    [10]
    MuX,WuX,HeW,et al.Pyroptosis and inflammasomes in diabetic wound healing[J].Front Endocrinol (Lausanne),2022,13:950798.DOI: 10.3389/fendo.2022.950798.
    [11]
    Al MamunA,ShaoC,GengP,et al.The mechanism of pyroptosis and its application prospect in diabetic wound healing[J].J Inflamm Res,2024,17:1481-1501.DOI: 10.2147/JIR.S448693.
    [12]
    LiuW,YuanY,LiuD.Extracellular vesicles from adipose-derived stem cells promote diabetic wound healing via the PI3K-AKT-mTOR-HIF-1α signaling pathway[J].Tissue Eng Regen Med,2021,18(6):1035-1044.DOI: 10.1007/s13770-021-00383-8.
    [13]
    SongY,YouY,XuX,et al.Adipose-derived mesenchymal stem cell-derived exosomes biopotentiated extracellular matrix hydrogels accelerate diabetic wound healing and skin regeneration[J].Adv Sci (Weinh),2023,10(30):e2304023.DOI: 10.1002/advs.202304023.
    [14]
    SidhomK,ObiPO,SaleemA.A review of exosomal isolation methods: is size exclusion chromatography the best option?[J].Int J Mol Sci,2020,21(18):6466.DOI: 10.3390/ijms21186466.
    [15]
    HouL,ZhangX,DuH.Advances in mesenchymal stromal cells and nanomaterials for diabetic wound healing[J].Diabetes Metab Res Rev,2023,39(4):e3638.DOI: 10.1002/dmrr.3638.
    [16]
    ChangM,NguyenTT.Strategy for treatment of infected diabetic foot ulcers[J].Acc Chem Res,2021,54(5):1080-1093.DOI: 10.1021/acs.accounts.0c00864.
    [17]
    DinhT,VevesA.Microcirculation of the diabetic foot[J].Curr Pharm Des,2005,11(18):2301-2309.DOI: 10.2174/1381612054367328.
    [18]
    Ramachandra BhatL,VedanthamS,KrishnanUM,et al.Methylglyoxal-an emerging biomarker for diabetes mellitus diagnosis and its detection methods[J].Biosens Bioelectron,2019,133:107-124.DOI: 10.1016/j.bios.2019.03.010.
    [19]
    KimJH,KimKA,ShinYJ,et al.Methylglyoxal induced advanced glycation end products (AGE)/receptor for AGE (RAGE)-mediated angiogenic impairment in bone marrow-derived endothelial progenitor cells[J].J Toxicol Environ Health A,2018,81(9):266-277.DOI: 10.1080/15287394.2018.1440185.
    [20]
    KimYH,TabataY.Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure[J].J Biomed Mater Res A,2016,104(4):942-956.DOI: 10.1002/jbm.a.35635.
    [21]
    IzadiR,HejaziSH,BahramikiaS.Injection of stem cells derived from allogeneic adipose tissue, a new strategy for the treatment of diabetic wounds[J].J Diabetes Complications,2023,37(7):108496.DOI: 10.1016/j.jdiacomp.2023.108496.
    [22]
    ZhangH,GuY,ZhangK,et al.Roles and mechanisms of umbilical cord mesenchymal stem cells in the treatment of diabetic foot: a review of preclinical and clinical studies[J].J Diabetes Complications,2024,38(1):108671.DOI: 10.1016/j.jdiacomp.2023.108671.
    [23]
    WeiL,XuY,ZhangL,et al.Mesenchymal stem cells promote wound healing and effects on expression of matrix metalloproteinases-8 and 9 in the wound tissue of diabetic rats[J].Stem Cells Dev,2023,32(1/2):25-31.DOI: 10.1089/scd.2021.0218.
    [24]
    UzunE,GüneyA,GönenZB,et al.Intralesional allogeneic adipose-derived stem cells application in chronic diabetic foot ulcer: phase I/2 safety study[J].Foot Ankle Surg,2021,27(6):636-642.DOI: 10.1016/j.fas.2020.08.002.
    [25]
    ShiR,JinY,CaoC,et al.Localization of human adipose-derived stem cells and their effect in repair of diabetic foot ulcers in rats[J].Stem Cell Res Ther,2016,7(1):155.DOI: 10.1186/s13287-016-0412-2.
    [26]
    CaiF,ChenW,ZhaoR,et al.The capacity of exosomes derived from adipose-derived stem cells to enhance wound healing in diabetes[J].Front Pharmacol,2023,14:1063458.DOI: 10.3389/fphar.2023.1063458.
    [27]
    KalluriR,LeBleuVS.The biology, function, and biomedical applications of exosomes[J].Science,2020,367(6478):eaau6977.DOI: 10.1126/science.aau6977.
    [28]
    TangT,ChenL,ZhangM,et al.Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery[J].Diabetol Metab Syndr,2024,16(1):37.DOI: 10.1186/s13098-023-01210-x.
    [29]
    TengL,MaqsoodM,ZhuM,et al.Exosomes derived from human umbilical cord mesenchymal stem cells accelerate diabetic wound healing via promoting M2 macrophage polarization, angiogenesis, and collagen deposition[J].Int J Mol Sci,2022,23(18):10421.DOI: 10.3390/ijms231810421.
    [30]
    FuS,ZhangH,LiX,et al.Exosomes derived from human amniotic mesenchymal stem cells facilitate diabetic wound healing by angiogenesis and enrich multiple lncRNAs[J].Tissue Eng Regen Med,2023,20(2):295-308.DOI: 10.1007/s13770-022-00513-w.
    [31]
    刘文剑,刘德伍.间充质干细胞来源细胞外囊泡促进糖尿病溃疡血管生成的研究进展[J].中华烧伤与创面修复杂志,2022,38(4):393-399.DOI: 10.3760/cma.j.cn501120-20201207-00520.
    [32]
    YuP,ZhangX,LiuN,et al.Pyroptosis: mechanisms and diseases[J].Signal Transduct Target Ther,2021,6(1):128.DOI: 10.1038/s41392-021-00507-5.
    [33]
    GuC,DragaD,ZhouC,et al.miR-590-3p inhibits pyroptosis in diabetic retinopathy by targeting NLRP1 and inactivating the NOX4 signaling pathway[J].Invest Ophthalmol Vis Sci,2019,60(13):4215-4223.DOI: 10.1167/iovs.19-27825.
    [34]
    YangK,LiuJ,ZhangX,et al.H3 relaxin alleviates migration, apoptosis and pyroptosis through P2X7R-mediated nucleotide binding oligomerization domain-like receptor protein 3 inflammasome activation in retinopathy induced by hyperglycemia[J].Front Pharmacol,2020,11:603689.DOI: 10.3389/fphar.2020.603689.
    [35]
    KongH,ZhaoH,ChenT,et al.Targeted P2X7/NLRP3 signaling pathway against inflammation, apoptosis, and pyroptosis of retinal endothelial cells in diabetic retinopathy[J].Cell Death Dis,2022,13(4):336.DOI: 10.1038/s41419-022-04786-w.
    [36]
    ShorningBY,DassMS,SmalleyMJ,et al.The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling[J].Int J Mol Sci,2020,21(12):4507.DOI: 10.3390/ijms21124507.
    [37]
    GoldbraikhD,NeufeldD,Eid-MutlakY,et al.USP1 deubiquitinates Akt to inhibit PI3K-Akt-FoxO signaling in muscle during prolonged starvation[J].EMBO Rep,2020,21(4):e48791.DOI: 10.15252/embr.201948791.
    [38]
    RezaeiS,NikpanjehN,RezaeeA,et al.PI3K/Akt signaling in urological cancers: tumorigenesis function, therapeutic potential, and therapy response regulation[J].Eur J Pharmacol,2023,955:175909.DOI: 10.1016/j.ejphar.2023.175909.
    [39]
    FontanaF,GiannittiG,MarchesiS,et al.The PI3K/Akt pathway and glucose metabolism: a dangerous liaison in cancer[J].Int J Biol Sci,2024,20(8):3113-3125.DOI: 10.7150/ijbs.89942.
    [40]
    AbidMR,GuoS,MinamiT,et al.Vascular endothelial growth factor activates PI3K/Akt/forkhead signaling in endothelial cells[J].Arterioscler Thromb Vasc Biol,2004,24(2):294-300.DOI: 10.1161/01.ATV.0000110502.10593.06.
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