Wnt/<b>β</b>连环蛋白信号通路在体表创面愈合中的作用机制研究进展

伍倩; 谭晓宇; 王怡佳; 程少文; 崔红旺; 姚江凌

doi:10.3760/cma.j.cn501225-20220816-00348

Wnt/β连环蛋白信号通路在体表创面愈合中的作用机制研究进展

doi: 10.3760/cma.j.cn501225-20220816-00348

1.
海南医学院，海口　　570105
2.
海南医学院第一附属医院急诊和创伤外科，海口　　570102

基金项目:

国家自然科学基金地区科学基金 82260373, 81860347

海南省自然科学基金 822QN463, 822MS174

海南省卫生健康行业科研项目 21A200062, 21A200231

海南医学院第一附属医院青年培育基金 HYYFYPY202005

海南医学院大学生创新创业训练计划项目 X202211810008

详细信息

通讯作者:
姚江凌，Email：yaojiangling917@126.com

计量
- 文章访问数: 454
- HTML全文浏览量: 72
- PDF下载量: 40
- 被引次数: 0
出版历程
- 收稿日期: 2022-08-16

Research advances on the mechanism of Wnt/β-catenin signaling pathway in body surface wound healing

1.
Hainan Medical University, Haikou 570105, China
2.
Department of Emergency and Trauma Surgery, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, China

Funds:

Regional Science Foundation of National Natural Science Foundation of China 82260373, 81860347

Natural Science Foundation of Hainan Province of China 822QN463, 822MS174

Research Project of Health Industry in Hainan Province of China 21A200062, 21A200231

Youth Development Fund of the First Affiliated Hospital of Hainan Medical University HYYFYPY202005

Innovative Entrepreneurship Training Program for Hainan Medical University College Students X202211810008

More Information

Corresponding author: Yao Jiangling, Email: yaojiangling917@126.com

摘要

摘要: 创面愈合是一个缓慢而复杂的生物学过程，包括炎症反应、细胞增殖分化和迁移、血管新生、细胞外基质沉积和组织重塑等。Wnt信号通路可分为经典通路和非经典通路，其中Wnt经典通路又称Wnt/β连环蛋白信号通路，其在细胞分化、迁移和组织稳态维持过程中发挥重要作用。许多炎症因子、生长因子等都参与该通路的上游调控。Wnt/β连环蛋白信号通路的激活在皮肤创面的发生、发展、再生、修复及相关治疗的过程中，起到了重要作用。该文综述了Wnt/β连环蛋白信号通路与创面愈合的关系，并总结了其对炎症反应、细胞增殖、血管新生、毛囊再生和皮肤纤维化等创面愈合重要过程的影响以及Wnt信号通路抑制因子在创面愈合中的作用。
- 皮肤 /
- Wnt信号通路 /
- 伤口愈合 /
- 细胞增殖 /
- β连环蛋白
Abstract: Wound healing is a slow and complex biological process, including inflammatory reaction, cell proliferation, cell differentiation, cell migration, angiogenesis, extracellular matrix deposition, tissue remodeling, and so on. Wnt signaling pathway can be divided into classical pathway and non-classical pathway. Wnt classical pathway, also known as Wnt/β-catenin signaling pathway, plays an important role in cell differentiation, cell migration, and maintenance of tissue homeostasis. Many inflammatory factors and growth factors are involved in the upstream regulation of this pathway. The activation of Wnt/β-catenin signaling pathway plays an important role in the occurrence, development, regeneration, repair and related treatment of skin wounds. This article review the relationship between Wnt/β-catenin signaling pathway and wound healing, meanwhile summarizes its effects on important processes of wound healing, such as inflammation, cell proliferation, angiogenesis, hair follicle regeneration, and skin fibrosis, as well as the role of inhibitors of Wnt signaling pathway in wound healing.
- Skin /
- Wnt signaling pathway /
- Wound healing /
- Cell proliferation /
- β-catenin protein
所有作者均声明不存在利益冲突

HTML全文

参考文献(44)

[1]	GurtnerGC,WernerS,BarrandonY,et al.Wound repair and regeneration[J].Nature,2008,453(7193):314-321.DOI: 10.1038/nature07039.
[2]	LiuHF,ZhangF,LineaweaverWC.History and advancement of burn treatments[J].Ann Plast Surg,2017,78(2 Suppl 1):S2-8.DOI: 10.1097/SAP.0000000000000896.
[3]	YingJH,WangQ,LuL,et al.Fermitin family homolog 2 (Kindlin-2) affects vascularization during the wound healing process by regulating the Wnt/β-catenin signaling pathway in vascular endothelial cells[J].Bioengineered,2021,12(1):4654-4665.DOI: 10.1080/21655979.2021.1957526.
[4]	BastakotyD,YoungPP.Wnt/β-catenin pathway in tissue injury: roles in pathology and therapeutic opportunities for regeneration[J].FASEB J,2016,30(10):3271-3284.DOI: 10.1096/fj.201600502R.
[5]	JereSW, HoureldNN. Regulatory processes of the canonical Wnt/β-catenin pathway and photobiomodulation in diabetic wound repair[J]. Int J Mol Sci, 2022, 23(8): 4210. DOI: 10.3390/ijms23084210.
[6]	NieXQ,ZhangH,ShiXJ,et al.Asiaticoside nitric oxide gel accelerates diabetic cutaneous ulcers healing by activating Wnt/β-catenin signaling pathway[J].Int Immunopharmacol,2020,79:106109.DOI: 10.1016/j.intimp.2019.106109.
[7]	AkcoraBÖ,StormG,BansalR.Inhibition of canonical WNT signaling pathway by β-catenin/CBP inhibitor ICG-001 ameliorates liver fibrosis in vivo through suppression of stromal CXCL12[J].Biochim Biophys Acta Mol Basis Dis,2018,1864(3):804-818.DOI: 10.1016/j.bbadis.2017.12.001.
[8]	SidhuGS,ManiH,GaddipatiJP,et al.Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice[J].Wound Repair Regen,1999,7(5):362-374.DOI: 10.1046/j.1524-475x.1999.00362.x.
[9]	WhyteJL,SmithAA,HelmsJA.Wnt signaling and injury repair[J].Cold Spring Harb Perspect Biol,2012,4(8):a008078.DOI: 10.1101/cshperspect.a008078.
[10]	StojadinovicO, BremH, VouthounisC, et al.Molecular pathogenesis of chronic wounds: the role of β-catenin and c-myc in the inhibition of epithelialization and wound healing[J]. Am J Pathol, 2005, 167(1): 59-69.DOI: 10.1016/S0002-9440(10)62953-7.
[11]	ZhangF,LiuY,WangSQ,et al. Inter-leukin-25-mediated‐IL-17RB upregulation promotes cutaneous wound healing in diabetic mice by improving endothelial cell functions[J].Front Immunol,2022,13:809755.DOI: 10.3389/fimmu.2022.809755.
[12]	BukowskaJ,WalendzikK,KopcewiczM,et al.Wnt signaling and the transcription factor Foxn1 contribute to cutaneous wound repair in mice[J].Connect Tissue Res,2021,62(2):238-248.DOI: 10.1080/03008207.2019.1688314.
[13]	WangZJ,LuH,TangT,et al.Tetrahedral framework nucleic acids promote diabetic wound healing via the Wnt signalling pathway[J].Cell Prolif,2022,55(11):e13316.DOI: 10.1111/cpr.13316.
[14]	ZhangB,WuXD,ZhangX,et al.Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/β-catenin pathway[J].Stem Cells Transl Med,2015,4(5):513-522.DOI: 10.5966/sctm.2014-0267.
[15]	WeiW,JiangF,LiuXC,et al.TMEM9 mediates IL-6 and IL-1β secretion and is modulated by the Wnt pathway[J].Int Immunopharmacol,2018,63:253-260.DOI: 10.1016/j.intimp.2018.07.036.
[16]	林志琥, 韩笑, 张孟瑶, 等. 阿司匹林通过调控Wnt/β-catenin信号通路抑制兔耳增生性瘢痕的生长[J]. 中南大学学报(医学版), 2022, 47(6): 698-706. DOI: 10.11817/j.issn.1672-7347.2022.220038.
[17]	SunQ,RabbaniP,TakeoM,et al.Dissecting Wnt signaling for melanocyte regulation during wound healing[J].J Invest Dermatol,2018,138(7):1591-1600.DOI: 10.1016/j.jid.2018.01.030.
[18]	HuelskenJ,VogelR,ErdmannB,et al.β-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin[J].Cell,2001,105(4):533-545.DOI: 10.1016/s0092-8674(01)00336-1.
[19]	MaB,HottigerMO.Crosstalk between Wnt/β-catenin and NF-κB signaling pathway during inflammation[J].Front Immunol,2016,7:378.DOI: 10.3389/fimmu.2016.00378.
[20]	JangJ,JungY,KimY,et al.LPS-induced inflammatory response is suppressed by Wnt inhibitors, Dickkopf-1 and LGK974[J].Sci Rep,2017,7:41612.DOI: 10.1038/srep41612.
[21]	ValléeA,LecarpentierY.Crosstalk between peroxisome proliferator-activated receptor gamma and the canonical Wnt/β-catenin pathway in chronic inflammation and oxidative stress during carcinogenesis[J].Front Immunol,2018,9:745.DOI: 10.3389/fimmu.2018.00745.
[22]	JangJ,JungY,ChaeS,et al.WNT/β-catenin pathway modulates the TNF-α-induced inflammatory response in bronchial epithelial cells[J].Biochem Biophys Res Commun,2017,484(2):442-449.DOI: 10.1016/j.bbrc.2017.01.156.
[23]	Amini-NikS, GlancyD, BoimerC, et al.Pax7 expressing cells contribute to dermal wound repair, regulating scar size through a β-catenin mediated process[J]. Stem Cells, 2011, 29(9): 1371-1379. DOI: 10.1002/stem.688.
[24]	BastakotyD,SaraswatiS,CatesJ,et al.Inhibition of Wnt/β-catenin pathway promotes regenerative repair of cutaneous and cartilage injury[J].FASEB J,2015,29(12):4881-4892.DOI: 10.1096/fj.15-275941.
[25]	YangHL,TsaiYC,KoriviM,et al.Lucidone promotes the cutaneous wound healing process via activation of the PI3K/AKT, Wnt/β-catenin and NF-κB signaling pathways[J].Biochim Biophys Acta Mol Cell Res,2017,1864(1):151-168.DOI: 10.1016/j.bbamcr.2016.10.021.
[26]	LiC,AnY,SunY,et al.Adipose mesenchymal stem cell-derived exosomes promote wound healing through the WNT/β-catenin signaling pathway in dermal fibroblasts[J].Stem Cell Rev Rep,2022,18(6):2059-2073.DOI: 10.1007/s12015-022-10378-0.
[27]	HeB,ChenJ,LiuL,et al.Knockdown of Tcf3 enhances the wound healing effect of bone marrow mesenchymal stem cells in rats[J].Biosci Rep,2019,39(8): BSR20180369.DOI: 10.1042/BSR20180369.
[28]	YueYL,LvWY,ZhangL,et al.MiR-147b influences vascular smooth muscle cell proliferation and migration via targeting YY1 and modulating Wnt/β-catenin activities[J].Acta Biochim Biophys Sin (Shanghai),2018,50(9):905-913.DOI: 10.1093/abbs/gmy086.
[29]	ZhangB,WangM,GongAH,et al.HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing[J].Stem Cells,2015,33(7):2158-2168.DOI: 10.1002/stem.1771.
[30]	WangKY,YamadaS,IzumiH,et al.Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice[J].PLoS One,2018,13(3):e0195156.DOI: 10.1371/journal.pone.0195156.
[31]	GaoJ,ZhangJY,XiaLH,et al.Up-regulation of caveolin 1 mediated by chitosan activates Wnt/β-catenin pathway in chronic refractory wound diabetic rat model[J].Bioengineered,2022,13(1):1388-1398.DOI: 10.1080/21655979.2021.2017625.
[32]	ShiY,WangS,YangRH,et al.ROS promote hypoxia-induced keratinocyte epithelial-mesenchymal transition by inducing SOX2 expression and subsequent activation of Wnt/β-catenin[J].Oxid Med Cell Longev,2022,2022:1084006.DOI: 10.1155/2022/1084006.
[33]	ZhengJH,ChenK,WangHF,et al.SIRT7 regulates the vascular smooth muscle cells proliferation and migration via Wnt/β-catenin signaling pathway[J].Biomed Res Int,2018,2018:4769596.DOI: 10.1155/2018/4769596.
[34]	YangP,LiSY,ZhangH,et al.LRG1 accelerates wound healing in diabetic rats by promoting angiogenesis via the Wnt/β-catenin signaling pathway[J].Int J Low Extrem Wounds,2022:15347346221081610[2022-08-16]. https://pubmed.ncbi.nlm.nih.gov/35188432/.DOI:10.1177/15347346221081610.[published online ahead of print].
[35]	WangXX, LiuYH, HeJ, et al.Regulation of signaling pathways in hair follicle stem cells[J/OL]. Burns Trauma, 2022, 10:tkac022[2022-08-16].https://pubmed.ncbi.nlm.nih.gov/35795256/.DOI: 10.1093/burnst/tkac022.
[36]	WhyteJL,SmithAA,LiuB,et al.Augmenting endogenous Wnt signaling improves skin wound healing[J].PLoS One,2013,8(10):e76883.DOI: 10.1371/journal.pone.0076883.
[37]	DongL,HaoHJ,LiuJJ,et al.A conditioned medium of umbilical cord mesenchymal stem cells overexpressing Wnt7a promotes wound repair and regeneration of hair follicles in mice[J].Stem Cells Int,2017,2017:3738071.DOI: 10.1155/2017/3738071.
[38]	RognoniE, GomezC, PiscoAO, et al.Inhibition of β-catenin signalling in dermal fibroblasts enhances hair follicle regeneration during wound healing[J]. Development, 2016, 143(14): 2522-2535. DOI: 10.1242/dev.131797.
[39]	BukowskaJ,WalendzikK,KopcewiczM,et al.Wnt signaling and the transcription factor Foxn1 contribute to cutaneous wound repair in mice[J].Connect Tissue Res,2021,62(2):238-248.DOI: 10.1080/03008207.2019.1688314.
[40]	HanNN,JiaL,SuYY,et al.Lactobacillus reuteri extracts promoted wound healing via PI3K/AKT/β-catenin/TGFβ1 pathway[J].Stem Cell Res Ther,2019,10(1):243.DOI: 10.1186/s13287-019-1324-8.
[41]	GayD,GhinattiG,Guerrero-JuarezCF,et al.Phagocytosis of Wnt inhibitor SFRP4 by late wound macrophages drives chronic Wnt activity for fibrotic skin healing[J].Sci Adv,2020,6(12):eaay3704.DOI: 10.1126/sciadv.aay3704.
[42]	ZhongYY,WangK,ZhangY,et al.Ocular Wnt/β-catenin pathway inhibitor XAV939-loaded liposomes for treating alkali-burned corneal wound and neovascularization[J].Front Bioeng Biotechnol,2021,9:753879.DOI: 10.3389/fbioe.2021.753879.
[43]	DeshmukhV,SeoT,O'GreenAL,et al.SM04755, a small-molecule inhibitor of the Wnt pathway, as a potential topical treatment for tendinopathy[J].J Orthop Res,2021,39(9):2048-2061.DOI: 10.1002/jor.24898.
[44]	XiongY,ChenL,YanCC,et al.Circulating exosomal miR-20b-5p inhibition restores Wnt9b signaling and reverses diabetes-associated impaired wound healing[J].Small,2020,16(3):e1904044.DOI: 10.1002/smll.201904044.