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Volume 42 Issue 1
Jan.  2026
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2026  >  42(1): 91-100
Gu Y,Chen YZ,Wang SY,et al.Proteomics analysis of the effect and mechanism of ADSCs on full-thickness skin defects in diabetic rats[J].Chin J Burns Wounds,2026,42(1):91-100.DOI: 10.3760/cma.j.cn501225-20240617-00236.
Citation: Gu Y,Chen YZ,Wang SY,et al.Proteomics analysis of the effect and mechanism of ADSCs on full-thickness skin defects in diabetic rats[J].Chin J Burns Wounds,2026,42(1):91-100.DOI: 10.3760/cma.j.cn501225-20240617-00236.
shu

Proteomics analysis of the effect and mechanism of ADSCs on full-thickness skin defects in diabetic rats

doi: 10.3760/cma.j.cn501225-20240617-00236
  • 1.

    Institute of Plastic Surgery, Shandong Second Medical University, Weifang 261053, China

  • 2.

    Department of Burn Plastic Surgery, Emergency General Hospital, Beijing 100028, China

  • 3.

    Medical Aesthetic Plastic Surgery Center, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276003, China

Funds:

General Program of Shandong Natural Science Foundation ZR2021MH338

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    Abstract
  •   Objective  To explore the effect and mechanism of adipose-derived mesenchymal stem cells (ADSCs) on full-thickness skin defects in diabetic rats using proteomics analysis.  Methods  This study was a self-control design experimental study. Four 8 to 10 weeks old male Sprague-Dawley rats were selected, and ADSCs were extracted from their epididymal adipose tissue and successfully identified. The third passage of ADSCs were used for the following experiments. Twenty-four 4 to 6 weeks old male Sprague-Dawley rats were selected and the type 2 diabetes model was successfully established. Among them, 16 diabetic rats weighing 350 to 400 g were chosen, and a full-thickness skin defect wound was created on each side of the spine on their backs at the same level. Using the random number table method, the two wounds of each rat were included in experimental group and control group (with 16 wounds in each group), and the cell suspensions containing ADSCs and phosphate buffered saline were injected at multiple points around and at the base of the wounds immediately after injury, respectively. The wound healing rates were calculated at day 7, 10, and 14 after injury in rats. At day 7 after injury in rats, wound tissue was collected and proteins were extracted. Four-dimensional data-independent acquisition label-free quantitative proteomics technology was used for quantitative proteomics analysis and bioinformatics analysis to screen differentially expressed proteins (DEPs) in the two groups of wound tissue. Then, key DEPs were screened through protein-protein interaction networks, gene ontology (GO) was used for functional annotation and enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) was used for pathway enrichment analysis to further screen target DEPs. The wound tissue of rats 7 days after injury was collected, and Western blotting was used to detect the protein expression of thymocyte differentiation antigen 1 (Thy-1) and G protein-coupled receptor 177/Wnt ligand secretion mediator (GPR177/Wls).  Results  At day 7, 10, and 14 after injury in rats, the wound healing rates in experimental group were (66±16)%, (83±8)%, and (93±4)%, respectively, which were significantly higher than (30±8)%, (62±6)%, and (77±8)% in control group (with t values of -4.41, -7.46, and -6.65, respectively, P<0.05). At day 7 after injury in rats, compared with those in control group, a total of 474 DEPs were screened from the wound tissue in experimental group (P<0.05). A total of 224 key DEPs were further screened out, among which 78 DEPs were significantly upregulated and 146 DEPs were significantly downregulated. GO functional annotation analysis showed that the most significantly upregulated and downregulated DEPs mainly affected protein expression under cellular processes and biological regulation conditions, and were related to cell anatomical entities and protein-containing complexes, as well as specific binding and catalytic activity between biomolecules. GO functional enrichment analysis showed that the most significantly upregulated DEPs were significantly enriched in Wnt-protein binding. KEGG pathway enrichment analysis showed that the significantly upregulated and downregulated DEPs were enriched in pathways such as starch and sucrose metabolism, nucleotide metabolism, p53 signaling pathway, and extracellular matrix -receptor interaction, and so on. A total of 4 target proteins were screened out, including Thy-1, GPR177/Wls, Fer/CIP4 homology domain only 2, and mitochondrial ribosomal protein L21, with the first two being significantly upregulated DEPs while the latter two being significantly downregulated DEPs. At day 7 after injury in rats, the protein expressions of GPR177/Wls and Thy-1 in the wound tissue in experimental group were 0.93±0.07 and 0.96±0.05, respectively, which were significantly higher than 0.39±0.07 and 0.36±0.12 in control group (with t values of 11.61 and 9.41, respectively, P<0.05).  Conclusions  Based on proteomics analysis, it was revealed that ADSCs from rats can promote the wound healing of full-thickness skin defects in diabetic rats by upregulating the protein expression of GPR177/Wls and Thy-1.

     

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    • References(40)
  • [1]
    NitzanO, EliasM, ChazanB, et al. Urinary tract infections in patients with type 2 diabetes mellitus: review of prevalence, diagnosis, and management[J]. Diabetes Metab Syndr Obes, 2015,8:129-136. DOI: 10.2147/DMSO.S51792.
    [2]
    AschnerP, KarurangaS, JamesS, et al. The International Diabetes Federation's guide for diabetes epidemiological studies[J]. Diabetes Res Clin Pract, 2021,172:108630. DOI: 10.1016/j.diabres.2020.108630.
    [3]
    中国老年2型糖尿病防治临床指南编写组,中国老年医学学会老年内分泌代谢分会,中国老年保健医学研究会老年内分泌与代谢分会,等 .中国老年2型糖尿病防治临床指南(2022年版)[J|.中华内科杂志,2022,61(1):12-50. DOI: 10.3760/cma.j.cn112138-20211027-00751.
    [4]
    LiuH, LiZ, ZhaoY, et al. Novel diabetic foot wound dressing based on multifunctional hydrogels with extensive temperature-tolerant, durable, adhesive, and intrinsic antibacterial properties[J]. ACS Appl Mater Interfaces, 2021,13(23):26770-26781. DOI: 10.1021/acsami.1c05514.
    [5]
    SchaperNC, van NettenJJ, ApelqvistJ, et al. Practical guidelines on the prevention and management of diabetes-related foot disease (IWGDF 2023 update)[J]. Diabetes Metab Res Rev, 2024,40(3):e3657. DOI: 10.1002/dmrr.3657.
    [6]
    JiangY, WangX, XiaL, et al. A cohort study of diabetic patients and diabetic foot ulceration patients in China[J]. Wound Repair Regen, 2015,23(2):222-230. DOI: 10.1111/wrr.12263.
    [7]
    ChoH, BlatchleyMR, DuhEJ, et al. Acellular and cellular approaches to improve diabetic wound healing[J]. Adv Drug Deliv Rev, 2019,146:267-288. DOI: 10.1016/j.addr.2018.07.019.
    [8]
    ArmstrongDG, SwerdlowMA, ArmstrongAA, et al. Five year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer[J]. J Foot Ankle Res, 2020,13(1):16. DOI: 10.1186/s13047-020-00383-2.
    [9]
    KongD, ZhuangX, WangD, et al. Umbilical cord mesenchymal stem cell transfusion ameliorated hyperglycemia in patients with type 2 diabetes mellitus[J]. Clin Lab, 2014,60(12):1969-1976. DOI: 10.7754/clin.lab.2014.140305.
    [10]
    LeiL, ZhangX, MaoY, et al. Statin therapy and bone marrow CD34+ cell frequency in type 2 diabetes mellitus: a cross-sectional study[J]. Int J Cardiol, 2014,175(1):214-216. DOI: 10.1016/j.ijcard.2014.04.248.
    [11]
    QiuX, LiuJ, ZhengC, et al. Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis[J]. Cell Prolif, 2020,53(8):e12830. DOI: 10.1111/cpr.12830.
    [12]
    YangJ, ChenZ, PanD, et al. Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration[J]. Int J Nanomedicine, 2020,15:5911-5926. DOI: 10.2147/IJN.S249129.
    [13]
    MaT, FuB, YangX, et al. Adipose mesenchymal stem cell-derived exosomes promote cell proliferation, migration, and inhibit cell apoptosis via Wnt/β-catenin signaling in cutaneous wound healing[J]. J Cell Biochem, 2019,120(6):10847-10854. DOI: 10.1002/jcb.28376.
    [14]
    XuF, XiangQ, HuangJ, et al. Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu[J]. Stem Cell Res Ther, 2019,10(1):106. DOI: 10.1186/s13287-019-1196-y.
    [15]
    MaT, SunJ, ZhaoZ, et al. A brief review: adipose-derived stem cells and their therapeutic potential in cardiovascular diseases[J]. Stem Cell Res Ther, 2017,8(1):124. DOI: 10.1186/s13287-017-0585-3.
    [16]
    SavageN. Proteomics: high-protein research[J]. Nature, 2015,527(7576):S6-S7. DOI: 10.1038/527S6a.
    [17]
    WangN, ZhuF, ChenL, et al. Proteomics, metabolomics and metagenomics for type 2 diabetes and its complications[J]. Life Sci, 2018,212:194-202. DOI: 10.1016/j.lfs.2018.09.035.
    [18]
    WangX, GuH, QinD, et al. Exosomal miR-223 contributes to mesenchymal stem cell-elicited cardioprotection in polymicrobial sepsis[J]. Sci Rep, 2015,5:13721. DOI: 10.1038/srep13721.
    [19]
    FriedensteinAJ, ChailakhjanRK, LalykinaKS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells[J]. Cell Tissue Kinet, 1970,3(4):393-403. DOI: 10.1111/j.1365-2184.1970.tb00347.x.
    [20]
    CaplanAI. Mesenchymal stem cells: time to change the name![J]. Stem Cells Transl Med, 2017,6(6):1445-1451. DOI: 10.1002/sctm.17-0051.
    [21]
    ZukPA, ZhuM, AshjianP, et al. Human adipose tissue is a source of multipotent stem cells[J]. Mol Biol Cell, 2002,13(12):4279-4295. DOI: 10.1091/mbc.e02-02-0105.
    [22]
    GentileP, GarcovichS. Advances in regenerative stem cell therapy in androgenic alopecia and hair loss: Wnt pathway, growth-factor, and mesenchymal stem cell signaling impact analysis on cell growth and hair follicle development[J]. Cells, 2019, 8(5):466. DOI: 10.3390/cells8050466.
    [23]
    白晓智,陶克,刘洋,等. 人脂肪间充质干细胞外泌体对脓毒症小鼠急性肺损伤的影响及其机制[J]. 中华烧伤与创面修复杂志,2024,40(12):1132-1142. DOI: 10.3760/cma.j.cn501225-20240927-00355.
    [24]
    MaziniL, RochetteL, AdmouB, et al. Hopes and limits of adipose-derived stem cells (ADSCs) and mesenchymal stem cells (MSCs) in wound healing[J]. Int J Mol Sci, 2020,21(4):1306. DOI: 10.3390/ijms21041306.
    [25]
    BariE, SilvestreDD, MastracciL, et al. GMP-compliant sponge-like dressing containing MSC lyo-secretome: proteomic network of healing in a murine wound model[J]. Eur J Pharm Biopharm, 2020,155:37-48. DOI: 10.1016/j.ejpb.2020.08.003.
    [26]
    姜敏敏. MSC与成纤维细胞的增殖及分化在创面愈合中的作用及其机制研究[D/OL].重庆:第三军医大学,2015[2024-06-17]. https://wap.cnki.net/touch/web/Dissertation/Article/1016042800.nh.html. https://wap.cnki.net/touch/web/Dissertation/Article/1016042800.nh.html
    [27]
    OuyangX, HanX, ChenZ, et al. Correction: MSC-derived exosomes ameliorate erectile dysfunction by alleviation of corpus cavernosum smooth muscle apoptosis in a rat model of cavernous nerve injury[J]. Stem Cell Res Ther, 2022,13(1):508. DOI: 10.1186/s13287-022-03190-7.
    [28]
    YuB, ShaoH, SuC, et al. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1[J]. Sci Rep, 2016,6:34562. DOI: 10.1038/srep34562.
    [29]
    LorenowiczMJ, KorswagenHC. Sailing with the Wnt: charting the Wnt processing and secretion route[J]. Exp Cell Res, 2009,315(16):2683-2689. DOI: 10.1016/j.yexcr.2009.06.015.
    [30]
    NusseR, CleversH. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities[J]. Cell, 2017,169(6):985-999. DOI: 10.1016/j.cell.2017.05.016.
    [31]
    KorenE, FeldmanA, YusupovaM, et al. Thy1 marks a distinct population of slow-cycling stem cells in the mouse epidermis[J]. Nat Commun, 2022,13(1):4628. DOI: 10.1038/s41467-022-31629-1.
    [32]
    AnZ, SabalicM, BloomquistRF, et al. A quiescent cell population replenishes mesenchymal stem cells to drive accelerated growth in mouse incisors[J]. Nat Commun, 2018,9(1):378. DOI: 10.1038/s41467-017-02785-6.
    [33]
    GargettCE. Identification and characterisation of human endometrial stem/progenitor cells[J]. Aust N Z J Obstet Gynaecol, 2006,46(3):250-253. DOI: 10.1111/j.1479-828X.2006.00582.x.
    [34]
    YovchevMI, GrozdanovPN, ZhouH, et al. Identification of adult hepatic progenitor cells capable of repopulating injured rat liver[J]. Hepatology, 2008,47(2):636-647. DOI: 10.1002/hep.22047.
    [35]
    SedovE, KorenE, ChopraS, et al. THY1-mediated mechanisms converge to drive YAP activation in skin homeostasis and repair[J]. Nat Cell Biol, 2022,24(7):1049-1063. DOI: 10.1038/s41556-022-00944-6.
    [36]
    Mendoza-ReinosoV, BeverdamA. Epidermal YAP activity drives canonical WNT16/β-catenin signaling to promote keratinocyte proliferation in vitro and in the murine skin[J]. Stem Cell Res, 2018,29:15-23. DOI: 10.1016/j.scr.2018.03.005.
    [37]
    NygaardR, YuJ, KimJ, et al. Structural basis of WLS/Evi-mediated Wnt transport and secretion[J]. Cell, 2021,184(1):194-206.e14. DOI: 10.1016/j.cell.2020.11.038.
    [38]
    HausmannG, BänzigerC, BaslerK. Helping Wingless take flight: how WNT proteins are secreted[J]. Nat Rev Mol Cell Biol, 2007,8(4):331-336. DOI: 10.1038/nrm2141.
    [39]
    MichauxG, BorgneRL. Sorting, recycling and WNT signaling: Wntless and retromer functions[J]. Med Sci (Paris), 2009,25(6/7):617-621. DOI: 10.1051/medsci/2009256-7617.
    [40]
    Franch-MarroX, WendlerF, GuidatoS, et al. Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex[J]. Nat Cell Biol, 2008,10(2):170-177. DOI: 10.1038/ncb1678.
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