缺氧与炎症在创面愈合中扮演的角色

魏在荣; 张演基; 王达利

doi:10.3760/cma.j.cn501225-20240111-00014

缺氧与炎症在创面愈合中扮演的角色

doi: 10.3760/cma.j.cn501225-20240111-00014

遵义医科大学附属医院烧伤整形外科，遵义　　563003

基金项目:

国家自然科学基金地区科学基金项目 82360445

省部共建协同创新中心项目 2020-39

遵义市科技计划项目 2021-3

贵州茅台医院科研与人才培养资金 2022-13

详细信息

通讯作者:
王达利，Email：daliwangzy@sina.com

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- 被引次数: 0
出版历程
- 收稿日期: 2024-01-11

Roles of hypoxia and inflammation in wound healing

Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China

Funds:

Regional Science Foundation Project of National Natural Science Foundation of China 82360445

Collaborative Innovation Center of Chinese Ministry of Education and Guizhou Province 2020-39

Science and Technology Plan Project of Zunyi City 2021-3

Scientific Research and Talent Training Funds of Kweichow Moutai Hospital 2022-13

More Information

Corresponding author: Wang Dali, Email: daliwangzy@sina.com

摘要

摘要: 创面愈合是一个复杂的生物学过程，缺氧和炎症是启动创面愈合和影响创面愈合进程的2个关键因素。缺氧诱导因子1α（HIF-1α）和核因子κB是缺氧和炎症环境下的重要调控因子，缺氧和炎症之间的相互作用本质上由HIF-1α和核因子κB信号通路所介导，二者失调导致的HIF-1α或核因子κB信号通路的异常表达均会影响创面微环境，导致创面异常愈合。该文讨论了缺氧和炎症对创面愈合的影响，强调了缺氧和炎症之间的相互协作对创面愈合的作用，以及二者失调对创面愈合质量的影响，并对目前缺氧和炎症信号通路的干预策略进行总结，同时对未来创面的治疗进行展望。
- 伤口愈合 /
- 炎症 /
- 低氧 /
- 缺氧诱导因子1
Abstract: Wound healing is a complex biological process. Hypoxia and inflammation are the two key factors that initiate wound healing and affect the wound healing process. Hypoxia-inducible factor-1α (HIF-1α) and nuclear factor κB are the important regulators of hypoxia and inflammation. The interaction between hypoxia and inflammation is essentially mediated by HIF-1α and nuclear factor κB signaling pathways. The abnormal expression of HIF-1α or nuclear factor κB signaling pathway caused by the imbalance of hypoxia and inflammation will affect the wound microenvironment and lead to abnormal wound healing. This paper discussed the effects of hypoxia and inflammation on wound healing, emphasized the role of cooperation between hypoxia and inflammation on wound healing and the effect of their imbalance on the quality of wound healing, summarized the current intervention strategies of hypoxia and inflammation signaling pathways, and prospected the treatment of wound in the future.
- Wound healing /
- Inflammation /
- Hypoxia /
- Hypoxia-inducible factor 1
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参考文献(43)

[1]	McGettrickAF, O'NeillLAJ.The role of HIF in immunity and inflammation[J].Cell Metab,2020,32(4):524-536.DOI: 10.1016/j.cmet.2020.08.002.
[2]	WilkinsonHN,HardmanMJ.Wound healing: cellular mechanisms and pathological outcomes[J].Open Biol,2020,10(9):200223.DOI: 10.1098/rsob.200223.
[3]	ZhangL,JinL,GuoJL,et al.Chronic intermittent hypobaric hypoxia enhances bone fracture healing[J].Front Endocrinol (Lausanne),2021,11:582670.DOI: 10.3389/fendo.2020.582670.
[4]	ChenLH,GaoYY,LiY, et al.Severe intermittent hypoxia modulates the macrophage phenotype and impairs wound healing through downregulation of HIF-2α[J].Nat Sci Sleep,2022,14:1511-1520.DOI: 10.2147/NSS.S382275.
[5]	BaiQ,GaoQ,HuFF, et al.Reoxygenation modulates the adverse effects of hypoxia on wound repair[J].Int J Mol Sci,2022,23(24):15832.DOI: 10.3390/ijms232415832.
[6]	GuanY,NiuH,LiuZT,et al.Sustained oxygenation accelerates diabetic wound healing by promoting epithelialization and angiogenesis and decreasing inflammation[J].Sci Adv,2021,7(35):eabj0153.DOI: 10.1126/sciadv.abj0153.
[7]	LeeP,ChandelNS,SimonMC.Cellular adaptation to hypoxia through hypoxia inducible factors and beyond[J].Nat Rev Mol Cell Biol,2020,21(5):268-283.DOI: 10.1038/s41580-020-0227-y.
[8]	AtriC,GuerfaliFZ,LaouiniD.Role of human macrophage polarization in Inflammation during infectious diseases[J].Int J Mol Sci,2018,19(6):1801.DOI: 10.3390/ijms19061801.
[9]	WuWJ,SuYC,HuCX, et al.Hypoxia-induced scleral HIF-2α upregulation contributes to rises in MMP-2 expression and myopia development in mice[J].Invest Ophthalmol Vis Sci,2022,63(8):2.DOI: 10.1167/iovs.63.8.2.
[10]	SteinerCA,CartwrightIM,TaylorCT,et al.Hypoxia-inducible factor as a bridge between healthy barrier function, wound healing, and fibrosis[J].Am J Physiol Cell Physiol,2022,323(3):C866-C878.DOI: 10.1152/ajpcell.00227.2022.
[11]	DuscherD,MaanZN,WhittamAJ, et al.Fibroblast-specific deletion of hypoxia inducible factor-1 critically impairs murine cutaneous neovascularization and wound healing[J].Plast Reconstr Surg,2015,136(5):1004-1013.DOI: 10.1097/PRS.0000000000001699.
[12]	TaiYC,ZhengLY,LiaoJ,et al.Roles of the HIF-1α pathway in the development and progression of keloids[J].Heliyon,2023,9(8):e18651.DOI: 10.1016/j.heliyon.2023.e18651.
[13]	周璇,金琳博,张一鸣.氧微环境对急慢性创面愈合影响的研究进展[J].临床外科杂志,2022,30(12):1112-1114.DOI: 10.3969/j.issn.1005-6483.2022.12.004.
[14]	MoR,ZhangH,XuY,et al.Transdermal drug delivery via microneedles to mediate wound microenvironment[J].Adv Drug Deliv Rev,2023,195:114753.DOI: 10.1016/j.addr.2023.114753.
[15]	RaziyevaK,KimY,ZharkinbekovZ, et al.Immunology of acute and chronic wound healing[J].Biomolecules,2021,11(5):700.DOI: 10.3390/biom11050700.
[16]	TangYY,WangDC,WangYQ,et al.Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: a comprehensive review[J].Front Immunol,2022,13:1073971.DOI: 10.3389/fimmu.2022.1073971.
[17]	Castro-AlcarazS,MiskolciV,KalasapudiB,et al.NF-kappa B regulation in human neutrophils by nuclear IκBα: correlation to apoptosis[J].J Immunol,2002,169(7):3947-3953.DOI: 10.4049/jimmunol.169.7.3947.
[18]	CramerT,YamanishiY,ClausenBE,et al.HIF-1alpha is essential for myeloid cell-mediated inflammation[J].Cell,2003,112(5):645-657.DOI: 10.1016/s0092-8674(03)00154-5.
[19]	CaiYX,ChenKL,LiuCS,et al.Harnessing strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns[J].Bioact Mater,2023,28:243-254.DOI: 10.1016/j.bioactmat.2023.04.019.
[20]	FengC,ShanMJ,XiaYJ,et al.Single-cell RNA sequencing reveals distinct immunology profiles in human keloid[J].Front Immunol,2022,13:940645.DOI: 10.3389/fimmu.2022.940645.
[21]	SeoudyWM,Mohy El DienSM,Abdel ReheemTA,et al.Macrophages of the M1 and M2 types play a role in keloids pathogenesis[J].Int Wound J,2023,20(1):38-45.DOI: 10.1111/iwj.13834.
[22]	XieJ,WuXW,ZhengS,et al.Aligned electrospun poly(L-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways[J].J Nanobiotechnology,2022,20(1):342.DOI: 10.1186/s12951-022-01549-9.
[23]	SiWX,XieW,DengWB,et al.Angiotensin Ⅱ increases angiogenesis by NF-κB-mediated transcriptional activation of angiogenic factor AGGF1[J].FASEB J,2018,32(9):5051-5062.DOI: 10.1096/fj.201701543RR.
[24]	TabruynSP,GriffioenAW.NF-kappa B: a new player in angiostatic therapy[J].Angiogenesis,2008,11(1):101-106.DOI: 10.1007/s10456-008-9094-4.
[25]	ZhouX,GuoYL,YangK,et al.The signaling pathways of traditional Chinese medicine in promoting diabetic wound healing[J].J Ethnopharmacol,2022,282:114662.DOI: 10.1016/j.jep.2021.114662.
[26]	ZhangJW,WuXQ,MaJD,et al.Hypoxia and hypoxia-inducible factor signals regulate the development, metabolism, and function of B cells[J].Front Immunol,2022,13:967576.DOI: 10.3389/fimmu.2022.967576.
[27]	ChenYL,GaberT.Hypoxia/HIF modulates immune responses[J].Biomedicines,2021,9(3):260.DOI: 10.3390/biomedicines9030260.
[28]	ZhangZH,HuangYX,ZhangJW,et al.Activation of NF-κB signaling pathway during HCG-induced VEGF expression in luteal cells[J].Cell Biol Int,2019,43(3):344-349.DOI: 10.1002/cbin.11090.
[29]	XuXW,GuSC,HuangX,et al.The role of macrophages in the formation of hypertrophic scars and keloids[J/OL].Burns Trauma,2020,8:tkaa006[2024-01-11]. https://pubmed.ncbi.nlm.nih.gov/32341919/.DOI: 10.1093/burnst/tkaa006.
[30]	SalehK,StrömdahlAC,RiesbeckK, et al.Inflammation biomarkers and correlation to wound status after full-thickness skin grafting[J].Front Med (Lausanne),2019,6:159.DOI: 10.3389/fmed.2019.00159.
[31]	ČomaM,FröhlichováL,UrbanL, et al.Molecular changes underlying hypertrophic scarring following burns involve specific deregulations at all wound healing stages (inflammation, proliferation and maturation)[J].Int J Mol Sci,2021,22(2):897.DOI: 10.3390/ijms22020897.
[32]	LeiR,LiJ,LiuF,et al.HIF-1α promotes the keloid development through the activation of TGF-β/Smad and TLR4/MyD88/NF-κB pathways[J].Cell Cycle,2019,18(23):3239-3250.DOI: 10.1080/15384101.2019.1670508.
[33]	QiuZK,ZhangMZ,ZhangWC,et al.Role of HIF-1α in pathogenic mechanisms of keloids[J].J Cosmet Dermatol,2023,22(5):1436-1448.DOI: 10.1111/jocd.15601.
[34]	HongYK,ChangYH,LinYC, et al.Inflammation in wound healing and pathological scarring[J].Adv Wound Care (New Rochelle),2023,12(5):288-300.DOI: 10.1089/wound.2021.0161.
[35]	LeeSY,KimEK,SeoHB, et al.IL-17 induced stromal cell-derived factor-1 and profibrotic factor in keloid-derived skin fibroblasts via the STAT3 pathway[J].Inflammation,2020,43(2):664-672.DOI: 10.1007/s10753-019-01148-1.
[36]	DingN,WeiB,FuXH,et al.Natural products that target the NLRP3 inflammasome to treat fibrosis[J].Front Pharmacol,2020,11:591393.DOI: 10.3389/fphar.2020.591393.
[37]	周正杰,李鑫.信使RNA药物修饰及其递送系统研究进展[J].浙江大学学报(医学版),2023,52(4):439-450.DOI: 10.3724/zdxbyxb-2023-0101.
[38]	ZhaoF,LangHX,WangZ, et al.Human novel microRNA seq-915_x4024 in keratinocytes contributes to skin regeneration by suppressing scar formation[J].Mol Ther Nucleic Acids,2019,14:410-423.DOI: 10.1016/j.omtn.2018.12.016.
[39]	WellsJA,KumruK.Extracellular targeted protein degradation: an emerging modality for drug discovery[J].Nat Rev Drug Discov,2024,23(2):126-140.DOI: 10.1038/s41573-023-00833-z.
[40]	YangJY,RuanYY,WangD,et al.VHL-recruiting PROTAC attenuates renal fibrosis and preserves renal function via simultaneous degradation of Smad3 and stabilization of HIF-2α[J].Cell Biosci,2022,12(1):203.DOI: 10.1186/s13578-022-00936-x.
[41]	WangW,LiuY,XiongLL,et al.Synthesis of lathyrol PROTACs and evaluation of their anti-inflammatory activities[J].J Nat Prod,2023,86(4):767-781.DOI: 10.1021/acs.jnatprod.2c00912.
[42]	JoshiM,DeyP,DeA.Recent advancements in targeted protein knockdown technologies-emerging paradigms for targeted therapy[J].Explor Target Antitumor Ther,2023,4(6):1227-1248.DOI: 10.37349/etat.2023.00194.
[43]	KannanMP,SreeramanS,SomalaCS,et al.Advancement of targeted protein degradation strategies as therapeutics for undruggable disease targets[J].Future Med Chem,2023,15(10):867-883.DOI: 10.4155/fmc-2023-0072.