Volume 42 Issue 5
May  2026
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Wu Y,Yin WH,Yu M,et al.Influence and mechanism of exosomes derived from rat bone marrow mesenchymal stem cells on rat Fbs under high glucose conditions[J].Chin J Burns Wounds,2026,42(5):467-476.DOI: 10.3760/cma.j.cn501225-20250402-00158.
Citation: Wu Y,Yin WH,Yu M,et al.Influence and mechanism of exosomes derived from rat bone marrow mesenchymal stem cells on rat Fbs under high glucose conditions[J].Chin J Burns Wounds,2026,42(5):467-476.DOI: 10.3760/cma.j.cn501225-20250402-00158.

Influence and mechanism of exosomes derived from rat bone marrow mesenchymal stem cells on rat Fbs under high glucose conditions

doi: 10.3760/cma.j.cn501225-20250402-00158
Funds:

Gansu Provincial Natural Science Foundation 22JR5RA692

Backbone and Young Talent Project of Gansu Provincial Health Commission GSWSQN2025-20

Gansu Provincial Clinical Medical Research Center for Burns and Wound Repair 21JR7RA674

Lanzhou Youth Science and Technology Talent Innovation Project 2024-QN-38

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  •   Objective  To investigate the influence and mechanism of exosomes derived from rat bone marrow mesenchymal stem cells (BMSCs) on rat fibroblasts (Fbs) under high glucose conditions, with the aim of exploring a potential novel strategy for the treatment of diabetic wounds.  Methods  This study was designed as grouped experimental study. The exosomes derived from BMSCs (BMSC-Exos) were extracted from the rat primary BMSCs and were identified successfully. The BMSC-Exos were divided into control group and high-glucose group. The BMSC-Exos in control group were cultured routinely, while the BMSC-Exos in high-glucose group were cultured in DMEM medium containing glucose at a final molarity of 30 mmol/L (hereinafter referred to as high-glucose medium). The eukaryotic mRNA sequencing was performed on BMSC-Exos in both groups, combined with multi-database prediction and enrichment analysis, differentially expressed genes that strongly interacted with the classical pyroptosis signaling pathway were screened and identified. The rat BMSCs of passages 1 to 3 were divided into microRNA-140-3p (miR-140-3p) mimic control group, miR-140-3p mimic group, miR-140-3p inhibitor control group, and miR-140-3p inhibitor group according to the random number table method, then the corresponding miR-140-3p mimic control, miR-140-3p mimic, miR-140-3p inhibitor control, and miR-140-3p inhibitor were transfected into cells, respectively, after 24 hours of culture. The BMSC-Exos were extracted at 24 hours post-transfection, and the expression of miR-140-3p in BMSC-Exos was detected by real-time fluorescence quantitative polymerase chain reaction. The rat Fbs in the logarithmic growth phase were divided into miR-140-3p mimic control group, miR-140-3p mimic group, miR-140-3p inhibitor control group, and miR-140-3p inhibitor group. After 24 hours of culture in high-glucose medium, the Fbs were added with the exosomes secreted by BMSCs after being transfected with miR-140-3p mimic control, miR-140-3p mimic, miR-140-3p inhibitor control, and miR-140-3p inhibitor, respectively (the same grouping and treatment below). At 24 hours post-transfection, the cell absorbance value was detected using cell counting kit-8, representing cell proliferation activity. The rat Fbs in the logarithmic growth phase were grouped and treated, then the cell migration rate at 24 hours after scratching was detected by scratch test. At 24 hours post-transfection, the protein expression levels of pyroptosis-related protein, including interleukin-1β (IL-1β), IL-18, NOD-like receptor pyrin domain-containing protein 3 (NLRP3), cysteine aspartic acid specific protease-1 (caspase-1), and gasdermin D in cells were detected by Western blotting. The sample size was 3.  Results  Compared with that in control group, the expressions of miR-140-3p and miR-542-5p were significantly upregulated in BMSC-Exos of high-glucose group. MiR-140-3p was identified as the differentially expressed gene that strongly interacted with the classical pyroptosis signaling pathway. At 24 hours post-transfection, the expression of miR-140-3p in BMSC-Exos of miR-140-3p mimic group was significantly higher than that in miR-140-3p mimic control group (P<0.05), and the expression of miR-140-3p in BMSC-Exos of miR-140-3p inhibitor group was significantly lower than that in miR-140-3p inhibitor control group (P<0.05). At 24 hours post-transfection, the absorbance value of Fbs in miR-140-3p mimic group was 0.940±0.031, which was significantly higher than 0.781±0.020 in miR-140-3p mimic control group (P<0.05); the absorbance value of Fbs in miR-140-3p inhibitor group was 0.510±0.041, which was significantly lower than 0.822±0.061 in miR-140-3p inhibitor control group (P<0.05). The Fb migration rate at 24 hours after scratching in miR-140-3p mimic group was significantly higher than that in miR-140-3p mimic control group (P<0.05), and the Fb migration rate at 24 hours after scratching in miR-140-3p inhibitor group was significantly lower than that in miR-140-3p inhibitor control group (P<0.05). At 24 hours post-transfection, the protein expressions of NLRP3, IL-18, IL-1β, caspase-1, and gasdermin D in Fbs of miR-140-3p mimic group were significantly lower than those in miR-140-3p mimic control group (P<0.05); the protein expressions of NLRP3, IL-18, IL-1β, caspase-1, and gasdermin D in Fbs of miR-140-3p inhibitor group were significantly higher than those in miR-140-3p inhibitor control group (P<0.05).  Conclusions  The rat BMSC-Exos can deliver miR-140-3p to promote the proliferation and migration of rat Fbs under high-glucose conditions, inhibit the expression of pyroptosis-related protein, and alleviate cell pyroptosis. This study provides a promising therapeutic target for diabetic wound repair.

     

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  • [1]
    WangZ, ZhaoF, XuC, et al. Metabolic reprogramming in skin wound healing[J/OL]. Burns Trauma, 2024, 12:tkad047[2025-04-02]. https://pubmed.ncbi.nlm.nih.gov/38179472/.DOI: 10.1093/burnst/tkad047.
    [2]
    GulerZ, RooversJP. Role of fibroblasts and myofibroblasts on the pathogenesis and treatment of pelvic organ prolapse[J]. Biomolecules,2022,12(1):94.DOI: 10.3390/biom12010094.
    [3]
    WengS, LaiQL, WangJ, et al. The role of exosomes as mediators of neuroinflammation in the pathogenesis and treatment of Alzheimer's disease[J]. Front Aging Neurosci,2022,14:899944. DOI: 10.3389/fnagi.2022.899944.
    [4]
    SunY, TaoQ, WuX, et al. The utility of exosomes in diagnosis and therapy of diabetes mellitus and associated complications[J]. Front Endocrinol (Lausanne), 2021,12:756581. DOI: 10.3389/fendo.2021.756581.
    [5]
    FioraniF,DomenisR,DallaE,et al.Ceramide releases exosomes with a specific miRNA signature for cell differentiation[J].Sci Rep,2023,13(1):10993.DOI: 10.1038/s41598-023-38011-1.
    [6]
    ForbesJM,CooperME.Mechanisms of diabetic complications[J].Physiol Rev,2013,93(1):137-188.DOI: 10.1152/physrev.00045.2011.
    [7]
    BeckmanJA, CreagerMA. Vascular complications of diabetes[J]. Circ Res,2016,118(11):1771-1785.DOI: 10.1161/CIRCRESAHA.115.306884.
    [8]
    ChenW, ChenK, XuZ, et al. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predict mortality in patients with diabetic foot ulcers undergoing amputations[J]. Diabetes Metab Syndr Obes,2021,14:821-829.DOI: 10.2147/DMSO.S284583.
    [9]
    RafiullahM, BenabdelkamelH, MasoodA, et al. Urinary proteome differences in patients with type 2 diabetes pre and post liraglutide treatment[J]. Curr Issues Mol Biol,2023,45(2):1407-1421.DOI: 10.3390/cimb45020092.
    [10]
    DoyleLM, WangMZ. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis[J]. Cells,2019,8(7):727.DOI: 10.3390/cells8070727.
    [11]
    KalluriR, LeBleuVS. The biology, function, and biomedical applications of exosomes[J]. Science,2020,367(6478):eaau6977.DOI: 10.1126/science.aau6977.
    [12]
    GuoX,SuiR,PiaoH.Exosomes-mediated crosstalk between glioma and immune cells in the tumor microenvironment[J].CNS Neurosci Ther,2023,29(8):2074-2085.DOI: 10.1111/cns.14239.
    [13]
    TianCM, YangMF, XuHM, et al. Mesenchymal stem cell-derived exosomes: novel therapeutic approach for inflammatory bowel diseases[J]. Stem Cells Int,2023,2023:4245704.DOI: 10.1155/2023/4245704.
    [14]
    FangY, TianS, PanY, et al. Pyroptosis: a new frontier in cancer[J]. Biomed Pharmacother,2020,121:109595.DOI: 10.1016/j.biopha.2019.109595.
    [15]
    XuYJ,ZhengL,HuYW,et al.Pyroptosis and its relationship to atherosclerosis[J].Clin Chim Acta,2018,476:28-37.DOI: 10.1016/j.cca.2017.11.005.
    [16]
    ShiJ, GaoW, ShaoF. Pyroptosis: gasdermin-mediated programmed necrotic cell death[J]. Trends Biochem Sci,2017,42(4):245-254.DOI: 10.1016/j.tibs.2016.10.004.
    [17]
    CollRC,RobertsonAA,ChaeJJ,et al.A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases[J].Nat Med,2015,21(3):248-255.DOI: 10.1038/nm.3806.
    [18]
    SunR, ZhengW, YangS, et al. In silico identification and validation of pyroptosis-related genes in Chlamydia respiratory infection[J]. Int J Mol Sci,2023,24(17):13570. DOI: 10.3390/ijms241713570.
    [19]
    LiuX,ZhangM,ZhuX,et al.Loss of FAM60A attenuates cell proliferation in glioma via suppression of PI3K/Akt/mTOR signaling pathways[J].Transl Oncol,2021,14(11):101196.DOI: 10.1016/j.tranon.2021.101196.
    [20]
    ChenQ, LiuY, DingX, et al. Bone marrow mesenchymal stem cell-secreted exosomes carrying microRNA-125b protect against myocardial ischemia reperfusion injury via targeting SIRT7[J]. Mol Cell Biochem,2020,465(1/2):103-114. DOI: 10.1007/s11010-019-03671-z.
    [21]
    HanL,WangS,LiJ,et al.Urinary exosomes from patients with diabetic kidney disease induced podocyte apoptosis via microRNA-145-5p/Srgap2 and the RhoA/ROCK pathway[J].Exp Mol Pathol,2023,134:104877.DOI: 10.1016/j.yexmp.2023.104877.
    [22]
    HashemiM, ZandiehMA, ZiaolhaghS, et al. Nrf2 signaling in diabetic nephropathy, cardiomyopathy and neuropathy: therapeutic targeting, challenges and future prospective[J]. Biochim Biophys Acta Mol Basis Dis,2023,1869(5):166714.DOI: 10.1016/j.bbadis.2023.166714.
    [23]
    YangM,LiuC,JiangN,et al.Fibroblast growth factor 21 in metabolic syndrome[J].Front Endocrinol (Lausanne),2023,14:1220426.DOI: 10.3389/fendo.2023.1220426.
    [24]
    LiuY, JiangP, QuY, et al. Exosomes and exosomal miRNAs: a new avenue for the future treatment of rheumatoid arthritis[J]. Heliyon,2024,10(6):e28127.DOI: 10.1016/j.heliyon.2024.e28127.
    [25]
    冯俊云,费潇,方邵一涵,等.人脂肪间充质干细胞来源细胞外囊泡对高糖诱导的人脐静脉内皮细胞焦亡的影响及其机制[J].中华烧伤与创面修复杂志,2025,41(3):258-267.DOI: 10.3760/cma.j.cn501225-20240120-00025.
    [26]
    何家乐,董鸿斐,黄茜,等.细胞焦亡在糖尿病创面愈合中的作用研究进展[J].中华烧伤与创面修复杂志,2024,40(8):785-791.DOI: 10.3760/cma.j.cn501225-20230829-00068.
    [27]
    LiuX,ZhangZ,RuanJ,et al.Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores[J].Nature,2016,535(7610):153-158.DOI: 10.1038/nature18629.
    [28]
    CodoAC, DavanzoGG, MonteiroLB, et al. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis-dependent axis[J]. Cell Metab,2020,32(3):437-446.e5.DOI: 10.1016/j.cmet.2020.07.007.
    [29]
    CongL,BaiY,GuoZ.The crosstalk among autophagy, apoptosis, and pyroptosis in cardiovascular disease[J].Front Cardiovasc Med,2022,9:997469.DOI: 10.3389/fcvm.2022.997469.
    [30]
    TangH,GongX,DaiJ,et al.The IRF1/GBP5 axis promotes osteoarthritis progression by activating chondrocyte pyroptosis[J].J Orthop Translat,2024,44:47-59.DOI: 10.1016/j.jot.2023.11.005.
    [31]
    WanJ,LiuD,PanS,et al.NLRP3-mediated pyroptosis in diabetic nephropathy[J].Front Pharmacol,2022,13:998574.DOI: 10.3389/fphar.2022.998574.
    [32]
    LiuB,HeR,ZhangL,et al.Inflammatory caspases drive pyroptosis in acute lung injury[J].Front Pharmacol,2021,12:631256.DOI: 10.3389/fphar.2021.631256.
    [33]
    ZhengZ,YangS,DaiW,et al.The role of pyroptosis in metabolism and metabolic disease[J].Biomed Pharmacother,2024,176:116863.DOI: 10.1016/j.biopha.2024.116863.
    [34]
    KayagakiN,StoweIB,LeeBL,et al.Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling[J].Nature,2015,526(7575):666-671.DOI: 10.1038/nature15541.
    [35]
    HartlJ, SerpasL, WangY, et al. Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus[J]. J Exp Med,2021,218(5):e20201138.DOI: 10.1084/jem.20201138.
    [36]
    LiX, XieX, LianW, et al. Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model[J]. Exp Mol Med,2018,50(4):1-14.DOI: 10.1038/s12276-018-0058-5.
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