miR-429 Affects Chronic Non-Healing Wound Repair through Wnt/β-catenin Pathway

doi:10.3870/j.issn.1672-8009.2026.04.005

Abstract

Abstract: Objective To investigate the effects of miR-429 on the healing of chronic non-healing wounds and the Wnt/β-catenin signaling pathway. Methods A total of 60 rats were randomly divided into 5 groups:blank control group,model group,negative control group(injected with antagomir NC),LV-429 group(injected with miR-429 antagomir lentivirus),and inhibitor group(injected with miR-429 antagomir lentivirus and Wnt/β-catenin signaling pathway inhibitor IWP-2).The wound healing rates in rats were assessed,and wound tissue samples were collected for measurement of miR-429 levels,as well as the protein expression of Wnt3a and β-catenin,and the expression of vascular endothelial growth factor A(VEGFA)and endothelial nitric oxide synthase(ENOS).Rat serum samples were collectedor measurement of the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α). Results Compared with that in the model group and the negative control group,the miR-429 expression level was reduced in the LV-429 group and the inhibitor group.Compared with the model group and the negative control group,in the LV-429 group,the wound healing rates,Wnt3a,β-catenin protein expression,and the positive expression rates of VEGFA and ENOS were all increased,while the IL-6 and TNF-α levels were both decreased(P<0.05).In the inhibitor group,the wound healing rate,Wnt3a and β-catenin protein expression,and the positive expression rates of VEGFA and ENOS were all decreased,while the IL-6 and TNF-α levels were both increased(P<0.05). Conclusion Inhibiting the expression of miR-429 can promote the repair of chronic refractory wounds,and this process is mediated by activating the Wnt/β-catenin signaling pathway.

Key words: miR-429, wound repair, Wnt/β-catenin signaling pathway, vascular endothelial growth factor A, endothelial nitric oxide synthase, wound healing rate, interleukin-6, tumor necrosis factor-α

CLC Number:

R339.1

HUANG Wenwen, MENG Li, XIE Hui, HU Shouyong, SHI Huafeng. miR-429 Affects Chronic Non-Healing Wound Repair through Wnt/β-catenin Pathway[J]. Journal of Medical Molecular Biology, 2026, 23(4): 406-411.

References

[1] 李晓辉,黄象艳.自体富血小板血浆在慢性难愈合创面治疗中的应用进展[J].山东医药,2023,63(4):107-110.
LI X H,HUANG X Y.Application progress of autologous platelet-rich plasma in the treatment of chronic refractory wounds[J].Shandong Med J,2023,63(4):107-110.
[2] WILSON M.Theuse of a synthetic hybrid-scale fiber matrix to treat difficult-to-heal wounds[J].Cureus,2023,15(12):e50405.
[3] 马慧可,李萍,陈佳,等.慢性难愈合创面“缸口”的形成机制和中医药治疗研究进展[J].医学研究杂志,2023,52(7):194-197.
MA H K,LI P,CHEN J,et al.Research progress on the formation mechanism and treatment of chronic refractory wounds with traditional Chinese medicine[J].J Med Res,2023,52(7):194-197.
[4] 熊元,曹发奇,刘梦非,等.2023创伤骨科慢性难愈性创面诊疗指南:治疗概要[J].临床外科杂志,2024,32(1):49-52.
XIONG Y,CAO F Q,LIU M F,et al.Trauma orthopedics chronic non-healing wound diagnosis and treatment guidelines 2023:Overview of treatment[J].J Clin Surg,2024,32(1):49-52.
[5] DORMERK J,GKOTSOULIAS E.The role of hemodynamic shear stress in healing chronic wounds[J].Wounds,2022,34(11):254-262.
[6] 张珂珂,黄国宝.miR-429对烧伤小鼠肺组织炎性反应和氧化应激的影响[J].河北医药,2024,46(3):330-334.
ZHANG K K,HUANG G B.Effect of miR-429 on inflammatory response and oxidative stress in lung tissue of burned mice[J].Hebei Med J,2024,46(3):330-334.
[7] 徐凤英,梁萍萍,廖若夷.基于Wnt/β-catenin信号通路探讨益气生肌合剂对慢性难愈性创面大鼠模型修复愈合的影响及作用机制[J].环球中医药,2023,16(3):453-459.
XU F Y,LIANG P P,LIAO R Y.To investigate the effect and mechanism of Yiqi Shengji mixture on the repair and healing of chronic refractory wound in rats based on Wnt/β-catenin signaling pathway[J].Glob Tradit Chin Med,2023,16(3):453-459.
[8] 左远娟,黄金梅,丘平,等.基于Wnt/β-catenin信号通路探讨MEBT/MEBO促进慢性难愈合创面愈合的机制[J].现代中西医结合杂志,2024,33(12):1622-1628.
ZUO Y J,HUANG J M,QIU P,et al.MEBT/MEBO promotes the healing of chronic refractory wounds via Wnt/β-catenin signaling pathway[J].Mod J Integr Tradit Chin West Med,2024,33(12):1622-1628.
[9] 张小峰.体表慢性难愈性创面住院患者的回顾性分析[D].西安:西安医学院,2023.
ZHANG X F.Retrospective analysis of inpatients with chronic refracyory surface wounds[D].Xi’an:Xi’an Medical University,2023.
[10] LIU W,GAO R,YANG C,et al.ECM-mimetic immunomodulatory hydrogel for methicillin-resistant Staphylococcus aureus-infected chronic skin wound healing[J].Sci Adv,2022,8(27):eabn7006.
[11] 骆渊城,朱滨,杨威,等.益气活血生肌方对难愈性创面愈合及血管再生的影响[J].中国医药导报,2023,20(12):30-34.
LUO Y C,ZHU B,YANG W,et al.Effect of Yiqi Huoxue Shengji Prescription on refractory wound healing and vessel regeneration[J].China Med Her,2023,20(12):30-34.
[12] SUN Y,DING S,FAN Y,et al.miR-429 inhibits the angiogenesis of human brain microvascular endothelial cells through SNAI2-mediated GSK-3β/β-catenin pathway[J].Comput Math Methods Med,2021,2021:6753926.
[13] CHEN S,WANG J,WANG J,et al.Wnt/β-catenin signaling pathway promotes abnormal activation of fibroblast-like synoviocytes and angiogenesis in rheumatoid arthritis and the intervention of Er Miao San[J].Phytomedicine,2023,120:155064.
[14] LIU H,ZHANG H,LIU X,et al.Pancreatic stellate cells exploitWnt/β-catenin/TCF7-mediated glutamine metabolism to promote pancreatic cancer cells growth[J].Cancer Lett,2023,555:216040.
[15] 肖雪飞,刘石,符艳,等.黄芪甲苷通过调控Wnt/β-catenin信号通路对人成纤维细胞凋亡和肌成纤维细胞转化的作用[J].湖南中医药大学学报,2024,44(12):2183-2192.
XIAO X F,LIU S,FU Y,et al.Effects of astragaloside-Ⅳ on human fibroblast apoptosis and myofibroblast transformation by regulating Wnt/β-catenin signaling pathway[J].J Tradit Chin Med Univ Hunan,2024,44(12):2183-2192.
[16] ZHANG L,LIU Q,MU Q,et al.miR-429 suppresses proliferation and invasion of breast cancer via inhibiting the Wnt/β-catenin signaling pathway[J].Thorac Cancer,2020,11(11):3126-3138.
[17] KHALED M L,BYKHOVSKAYA Y,YABLONSKI S E R,et al.Differential expression of coding and long noncoding RNAs in keratoconus-affected corneas[J].Invest Ophthalmol Vis Sci,2018,59(7):2717-2728.
[18] LI B,ZHANG Y,YIN R,et al.Activating CD137 signaling promotes sprouting angiogenesis via increased VEGFA secretion and the VEGFR2/Akt/ENOS pathway[J].Mediators Inflamm,2020,2020:1649453.
[19] 王双勋,李大勇.基于Wnt/β-catenin通路探讨拔毒生肌散对糖尿病大鼠皮肤溃疡愈合的促进作用[J].中华中医药学刊,2023,41(2):115-119,266-267.
WANG S X,LI D Y.Promoting effect of Badu Shengji Powder on skin ulcer healing in diabetic rats based on Wnt/β-catenin pathway[J].Chin Arch Tradit Chin Med,2023,41(2):115-119,266-267.
[20] YANG Y,HUANG P,YANG J,et al.Therapeutic effect and concomitant toxicity of hydrargyrumchloratum compositum on chronic difficult-to-heal wounds in rats[J].J Ethnopharmacol,2025,347:119749.