Effects of High Glucose on Immune Cells and Growth Factors in Diabetic Foot Ulcer

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  • 1.Institute of Traditional Chinese Medicine Guangdong Pharmaceutical University Guangdong Guangzhou 511436, China
    2.The Second Affiliated Hospital of Tianjin University of Chinese Medicine Tianjin 300250, China
    3.TCM Institute of Sore and Ulcer Tianjin University of Traditional Chinese Medicine Tianjin 300250, China
    4.Tianjin Institute of Traditional Chinese Medicine Surgery Tianjin 300250, China

Received date: 2024-12-20

  Revised date: 2025-05-08

  Accepted date: 2025-05-09

  Online published: 2025-07-23

Abstract

Diabetic foot ulcer DFU is one of the main complications in the late stage of diabetes mellitus which is characterized by a long treatment cycle high amputation rate and high mortality rate and brings huge economic pressure and mental burden to patients. It is of particular importanse to explore the disease characteristics of DFU and improve the treatment efficiency of DFU. High-glucose environment is one of the important reasons for the difficult healing of DFU wounds. High-glucose has an important effect on immune cells and growth factors in foot ulcer wounds. In high-glucose environments the immune cell function of patients with DFU decreases significantly and the activity of key immune cells such as macrophages and T-cells which promote wound healing decreases while the expression level of inhibitory immune cells is elevated resulting in an imbalance of overall immune regulation. Which was manifested in impaired phagocytosis of neutrophils overexpression of NET decreased dendritic cell density prolonged excitability of M1 cells imbalance of T-cell ratios and imbalance of B-cell subpopulations. Growth factors play an important role in the ulcer repair process in which the release of pro-inflammatory growth factors such as IL-6 and TNF-α was significantly increased while the expression of VEGF TGF-β PDGF FGF and KGF show a decreasing trend. The abnormal immune cell function as well as the imbalance of growth factor expression directly contributed to the difficult healing nature of DFUs. This study reviews the effects of high glucose on immune cells and growth factors in foot ulcer wounds for providing new ideas of clinical treatment of DFU.


Cite this article

LIU Wei, ZHANG Zhaohui .

Effects of High Glucose on Immune Cells and Growth Factors in Diabetic Foot Ulcer

[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2025 , 27(5) : 470 -475 . DOI: magtech.2024.12.20-00001

References

       [1 Armstrong DG Tan TW Boulton AJM et al. Diabetic foot ulcersa reviewJ.JAMA20233301):62-75.

         2  Jhamb S Vangaveti VN Malabu UH. Genetic and molecular basis of diabetic foot ulcersclinical reviewJ.J Tissue Viability2016254):229-236.

         3  王雪,王伟,王萍,等.糖尿病足感染患者血清miRNA表达与创面修复因子及免疫功能的关系[J.中华医院感染学杂志,20213122):3422-3426.

         4  Linnemann C Şahin F Li N et al. Insulin can delay neutrophil extracellular trap formation in vitro-implication for diabetic wound care?[J.Biology Basel),2023128):1082.

         5  Tsirogianni AK Moutsopoulos NM Moutsopoulos HM. Wound healing immunological aspectsJ.Injury200637Suppl 1):S5-12.

         6  Melbouci D Haidar Ahmad A Decker P. Neutrophil extracellular traps NET): not only antimicrobial but also modulators of innate and adaptive immunities in inflammatory autoimmune diseasesJ.RMD Open202393):e003104.

         7  Pittman K Kubes P. Damage-associated molecular patterns control neutrophil recruitmentJ.J Innate Immun20135315-323.

         8  Soehnlein O Wantha S Simsekyilmaz S et al. Neutrophil-derived cathelicidin protects from neointimal hyperplasiaJ.Sci Transl Med20113103):103ra98.

         9  Wang J. Neutrophils in tissue injury and repairJ.Cell Tissue Res20183713):531-539.

         10 张延梅,严瑞明,丁玫琳,等.树突状细胞TLR2阻断抑制自身免疫性糖尿病研究[J.中国免疫学杂志,2019358):902-905911.

         11 蔺莉,徐旭英.专职吞噬细胞胞葬功能在慢性创面修复中的作用机制及应用[J/OL.海南医学院学报,1-142024-06-12.

         12 Adamson R. Role of macrophages in normal wound healing an overviewJ.J Wound Care2009188):349-351.

         13 黄仁燕,韩强,胡啸明,等.巨噬细胞在糖尿病足溃疡愈合过程中调控机制研究进展[J.海南医学院学报,2019254):315-320.

         14 许诏华,师建平.糖尿病创面愈合中巨噬细胞极化表观遗传学调控的研究进展[J.中国糖尿病杂志,2024322):145-148.

         15 Louiselle AE Niemiec SM Zgheib C et al. Macrophage polarization and diabetic wound healingJ.Transl Res2021236109-116.

         16 Ma H Ke Y Li Q et al. Bovine and human insulin activate CD8+-autoreactive CTLexpressing both type 1 and type 2 cytokines in C57BL/6 miceJ.J Immunol20001641):86-92.

         17 Park JE Barbul A. Understanding the role of immune regulation in wound healingJ. Am J Surg20041875A):11S-16S.

         18 Li B Wang JH. Fibroblasts and myofibroblasts in wound healing force generation and measurementJ.J Tissue Viability2011204):108-120.

         19 郭少英,闫建军,李媛,等.桃红四物汤对缺糖缺氧大鼠脑微血管内皮细胞VEGFVEGFR-2Akt基因及蛋白表达的作用机制研究[J.现代生物医学进展,2024244):636-640.

         20 潘冠华,阿迪力·萨来,等.NF-κB介导VEGF-A促进食管鳞状细胞癌血管生长和细胞增殖的实验研究[J.川北医学院学报,2024395):583-588.

         21 田佳庆,韦雨柔,肖方骏,等.虎杖苷调控HIF-1α/VEGF信号通路对绝经后骨质疏松症大鼠H型血管生成的影响[J.中成药,2024465):1672-1676.

         22 骆燕洪,田宇,武云凤,等.骨化三醇通过磷脂酰肌醇3激酶/蛋白激酶B信号通路改善高糖诱导的血管内皮细胞损伤的研究[J.中国糖尿病杂志,2024324):291-298.

         23 Geng K Ma X Jiang Z et al. WDR74 facilitates TGF-β/Smad pathway activation to promote M2 macrophage polarization and diabetic foot ulcer wound healing in miceJ.Cell Biol Toxicol2023394):1577-1591.

         24 Zhao Q Xu J Han X et al. Growth differentiation factor 10 induces angiogenesis to promote wound healing in rats with diabetic foot ulcers by activating TGF-β1/Smad3 signaling pathwayJ.Front Endocrinol Lausanne),2023131013018.

         25 蔡小艳,符茂雄.糖尿病足创面皮肤基质相关细胞因子研究进展[J.现代医药卫生,20223812):2055-2059.

         26 Zubair M Ahmad J. Role of growth factors and cytokines in diabetic foot ulcer healing a detailed reviewJ.Rev Endocr Metab Disord2019202):207-217.

         27 Presta M Chiodelli P Giacomini A et al. Fibroblast growth factors FGFs in cancer FGF traps as a new therapeutic approachJ.Pharmacol Ther2017179171-187.

         28 宗宪磊,曹春艳,宋国栋,等.角质细胞生长因子活性短肽促进糖尿病大鼠创面愈合的实验研究[J.中国医药导报,20181530):4-7.

         29 Peng Y Wu S Tang Q et al. KGF-1 accelerates wound contraction through the TGF-β1/Smad signaling pathway in a double-paracrine mannerJ.J Biol Chem201929421):8361-8370.

         30 Xiaojie W Banda J Qi H et al. Scarless wound healing Current insights from the perspectives of TGF-β KGF-1 and KGF-2J.Cytokine Growth Factor Rev20226626-37.

         31 Top C Yildiz S Oncul O et al. Phagocytic activity of neutrophils improves over the course of therapy of diabetic foot infectionsJ.J Infect2007554):369-373.

         32 Huang W Jiao J Liu J et al. MFG-E8 accelerates wound healing in diabetes by regulating "NLRP3 inflammasome-neutrophil extracellular traps" axisJ.Cell Death Discov2020684.

         33 Basyreva LY Shmeleva EV Ivanov VA et al. The effect of vitamin D3 on neutrophil extracellular trap formation in high-glucose conditionsJ.Bull Exp Biol Med20231762):137-142.

         34 Strom A Brüggemann J Ziegler I et al. Pronounced reduction of cutaneous Langerhans cell density in recently diagnosed type 2 diabetesJ.Diabetes2014633):1148-1153.

         35 Rahmannia M Amini A Chien S et al. Impact of photobiomodulation on macrophages and their polarization during diabetic wound healing a systematic reviewJ.Lasers Med Sci2022377):2805-2815.

         36 李晓春,吴建能,张华珍,等.糖尿病足与T淋巴细胞亚群的相关性研究[J.海南医学,20132411):1628-1630.

         37 盛宏光,金惠.2型糖尿病与流式细胞CD系列关系探讨[J.浙江预防医学,2001137):53-54.

         38 Deng C Xiang Y Tan T et al. Altered peripheral B-lymphocyte subsets in type 1diabetes and latent autoimmune diabetes in adultsJ.Diabetes Care2016393):434-440.

         39 Wan R Weissman JP Grundman K et al. Diabetic wound healingthe impact of diabetes on myofibroblast activity and its potential therapeutic treatmentsJ.Wound Repair Regen2021294):573-581.

         40 Liu Y Liu Y He W et al. Fibroblastsimmunomodulatory factors in refractory diabetic wound healingJ.Front Immunol202213918223.

         41 Monika P Waiker PV Chandraprabha MN et al. Myofibroblast progeny in wound biology and wound healing studiesJ. Wound Repair Regen2021294):531-547.

         42 齐淑静,付改霞,齐瑞霞.小檗碱调节HIF-1α/VEGF信号通路对皮肤溃疡大鼠血管生成和创面愈合的影响[J.陕西医学杂志,2024532):173-178.

         43 刘博研,赵锦.PDGFFGF-21APN2型糖尿病足患者中的表达及意义[J.中国实验诊断学,2023276):683-686.

         44 Shi R Lian W Han S et al. Nanosphere-mediated co-delivery of VEGF-A and PDGF-B genes for accelerating diabetic foot ulcers healing in ratsJ.Gene Ther2018256):425-438.

         45 陈芳,孙付宝,陈小将,等.糖尿病足患者血清VEGFbFGF水平与下肢血管病变程度的关系[J.临床和实验医学杂志,20212017):1856-1859.

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