Volume 38 Issue 12
Dec.  2022
Turn off MathJax
Article Contents
Cao P,Wang YW,Guan H,et al.Effects of mechanical tension on the formation of hypertrophic scars in rabbit ears and transforming growth factor-β1/Smad signaling pathway[J].Chin J Burns Wounds,2022,38(12):1162-1169.DOI: 10.3760/cma.j.cn501120-20211213-00412.
Citation: Cao P,Wang YW,Guan H,et al.Effects of mechanical tension on the formation of hypertrophic scars in rabbit ears and transforming growth factor-β1/Smad signaling pathway[J].Chin J Burns Wounds,2022,38(12):1162-1169.DOI: 10.3760/cma.j.cn501120-20211213-00412.

Effects of mechanical tension on the formation of hypertrophic scars in rabbit ears and transforming growth factor-β1/Smad signaling pathway

doi: 10.3760/cma.j.cn501120-20211213-00412
Funds:

General Program of National Natural Science Foundation of China 82172209

More Information
  • Corresponding author: Yao Ming, Email: nxsnake@126.com
  • Received Date: 2021-12-13
  •   Objective  To explore the effects of mechanical tension on the formation of hypertrophic scars in rabbit ears and transforming growth factor-β1 (TGF-β1)/Smad signaling pathway.  Methods  The experimental research method was adopted. Six New Zealand white rabbits, male or female, aged 3-5 months were used and 5 full-thickness skin defect wounds were made on the ventral surface of each rabbit ear. The appearance of all rabbit ear wounds was observed on post surgery day (PSD) 0 (immediately), 7, 14, 21, and 28. On PSD 28, the scar formation rate was calculated. Three mature scars in the left ear of each rabbit were included in tension group and the arch was continuously expanded with a spiral expander. Three mature scars in the right ear of each rabbit were included in sham tension group and only the spiral expander was sutured without expansion. There were 18 scars in each group. After mechanical tension treatment (hereinafter referred to as treatment) for 40 days, the color and texture of scar tissue in the two groups were observed. On treatment day 40, the scar elevation index (SEI) was observed and calculated; the histology was observed after hematoxylin eosin staining, and the collagen morphology was observed after Masson staining; mRNA expressions of TGF-β1, Smad3, collagen Ⅰ, collagen Ⅲ, and α-smooth muscle actin (α-SMA) in scar tissue were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction; and the protein expressions of TGF-β1, collagen Ⅰ, collagen Ⅲ, and α-SMA, and phosphorylation level of Smad3 in scar tissue were detected by Western blotting. The number of samples of each group in the experiments was 3. Data were statistically analyzed with independent sample t test.  Results  On PSD 0, 5 fresh wounds were formed on all the rabbit ears; on PSD 7, the wounds were scabbed; on PSD 14, most of the wounds were epithelialized; on PSD 21, all the wounds were epithelialized; on PSD 28, obvious hypertrophic scars were formed. The scar formation rate was 75% (45/60) on PSD 28. On treatment day 40, the scar tissue of rabbit ears in tension group was more prominent than that in sham tension group, the scar tissue was harder and the color was more ruddy; the SEI of the scar tissue of rabbit ears in tension group (2.02±0.08) was significantly higher than 1.70±0.08 in sham tension group (t=5.07, P<0.01). On treatment day 40, compared with those in sham tension group, the stratum corneum of scar tissue became thicker, and a large number of new capillaries, inflammatory cells, and fibroblasts were observed in the dermis, and collagen was more disordered, with nodular or swirling distribution in the scar tissue of rabbit ears in tension group. On treatment day 40, the mRNA expressions of TGF-β1, Smad3, collagen Ⅰ, collagen Ⅲ, and α-SMA in the scar tissue of rabbit ears in tension group were respectively 1.81±0.25, 5.71±0.82, 7.86±0.56, 4.35±0.28, and 5.89±0.47, which were significantly higher than 1.00±0.08, 1.00±0.12, 1.00±0.13, 1.00±0.14, and 1.00±0.14 in sham tension group (with t values of 5.36, 9.82, 20.60, 18.26, and 17.13, respectively, all P<0.01); the protein expressions of TGF-β1, collagen Ⅰ, collagen Ⅲ, and α-SMA, and phosphorylation level of Smad3 in the scar tissue of rabbit ears in tension group were respectively 0.865±0.050, 0.895±0.042, 0.972±0.027, 1.012±0.057, and 0.968±0.087, which were significantly higher than 0.657±0.050, 0.271±0.029, 0.631±0.027, 0.418±0.023, and 0.511±0.035 in sham tension group (with t values of 5.08, 21.27, 15.55, 16.70, and 8.40, respectively, all P<0.01).  Conclusions  Mechanical tension can inhibit the regression of hypertrophic scars in rabbit ears through stimulating the hyperplasia of scars, inhibiting the normal arrangement of dermal collagen fibers, and intensifying the deposition of collagen fibers, and the mechanism may be related to the activation of TGF-β1/Smad signaling pathway by mechanical tension.

     

  • loading
  • [1]
    YuanB, UptonZ, LeavesleyD, et al. Vascular and collagen target: a rational approach to hypertrophic scar management[J]. Adv Wound Care (New Rochelle), 2022,12(1):38-55. DOI: 10.1089/wound.2020.1348.
    [2]
    TuLX, LinZW, HuangQ, et al. USP15 enhances the proliferation, migration, and collagen deposition of hypertrophic scar-derived fibroblasts by deubiquitinating TGF-βR1 in vitro[J]. Plast Reconstr Surg, 2021,148(5):1040-1051. DOI: 10.1097/PRS.0000000000008488.
    [3]
    SharpPA, PanB, YakuboffKP, et al. Development of a best evidence statement for the use of pressure therapy for management of hypertrophic scarring[J]. J Burn Care Res, 2016,37(4): 255-264. DOI: 10.1097/BCR.0000000000000253.
    [4]
    GuSC, HuangX, XuXW, et al. Inhibition of CUB and sushi multiple domains 1 (CSMD1) expression by miRNA-190a-3p enhances hypertrophic scar-derived fibroblast migration in vitro[J]. BMC Genomics, 2021,22(1): 613. DOI: 10.1186/s12864-021-07920-8.
    [5]
    TejiramS, ZhangJ, TravisTE, et al. Compression therapy affects collagen type balance in hypertrophic scar[J]. J Surg Res, 2016,201(2):299-305. DOI: 10.1016/j.jss.2015.10.040.
    [6]
    ZhangZW, HuangX, YangJH, et al. Identification and functional analysis of a three-miRNA ceRNA network in hypertrophic scars[J]. J Transl Med, 2021,19(1): 451. DOI: 10.1186/s12967-021-03091-y.
    [7]
    MengXX,YuZX,XuWY, et al. Control of fibrosis and hypertrophic scar formation via glycolysis regulation with IR780[J/OL].Burns Trauma,2022,10:tkac015[2021-12-13]. https://pubmed.ncbi.nlm.nih.gov/35769829/.DOI: 10.1093/burnst/tkac015.
    [8]
    KravezE, VilligerM, BoumaB, et al. Prediction of scar size in rats six months after burns based on early post-injury polarization-sensitive optical frequency domain imaging[J]. Front Physiol, 2017,8:967. DOI: 10.3389/fphys.2017.00967.
    [9]
    RuZ,HuY,HuangSH,et al.Bioflavonoid Galangin suppresses hypertrophic scar formation by the TGF-β/Smad signaling pathway[J].Evid Based Complement Alternat Med,2021,2021:2444839.DOI: 10.1155/2021/2444839.
    [10]
    SohrabiC,GoutosI.The use of botulinum toxin in keloid scar management: a literature review[J].Scars Burn Heal,2020,6:2059513120926628.DOI: 10.1177/2059513120926628.
    [11]
    TanJL,WuJ. Current progress in understanding the molecular pathogenesis of burn scar contracture[J/OL].Burns Trauma,2017,5:14[2021-12-13]. https://pubmed.ncbi.nlm.nih.gov/28546987/.DOI: 10.1186/s41038-017-0080-1.
    [12]
    WongVW, RustadKC, AkaishiS, et al. Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling[J]. Nat Med, 2011,18(1):148-152. DOI: 10.1038/nm.2574.
    [13]
    ShaoT,TangW,LiY,et al.Research on function and mechanisms of a novel small molecule WG449E for hypertrophic scar[J].J Eur Acad Dermatol Venereol,2020,34(3):608-618.DOI: 10.1111/jdv.16028.
    [14]
    JiXJ, TangZ, ShuaiWW, et al. Endogenous peptide LYENRL prevents the activation of hypertrophic scar-derived fibroblasts by inhibiting the TGF-β1/Smad pathway[J]. Life Sci, 2019,231:116674. DOI: 10.1016/j.lfs.2019.116674.
    [15]
    李荟元, 刘建波, 兰海. 建立增生性瘢痕动物实验模型[J]. 第四军医大学学报, 1998,19(6):655-657.
    [16]
    李荟元,刘建波,夏炜,等.增生性瘢痕动物实验模型的建立与应用[J].中华整形外科杂志,2001,17(5):276-278,插图5-1.DOI: 10.3760/j.issn:1009-4598.2001.05.006.
    [17]
    李希军,柳大烈,王吉慧.兔耳增生性瘢痕模型建立方法的探讨[J].中国美容医学,2006,15(5):499-500,中插1.DOI: 10.3969/j.issn.1008-6455.2006.05.006.
    [18]
    PaternoJ, VialIN, WongVW, et al. Akt-mediated mechanotransduction in murine fibroblasts during hypertrophic scar formation[J]. Wound Repair Regen, 2011,19(1):49-58. DOI: 10.1111/j.1524-475X.2010.00643.x.
    [19]
    AarabiS, BhattKA, ShiY, et al. Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis[J]. FASEB J, 2007,21(12): 3250-3261. DOI: 10.1096/fj.07-8218com.
    [20]
    李虎,李小静,宁金龙,等.兔耳增生性瘢痕模型的建立及微血管构筑在病理性瘢痕形成和发展过程中的意义[J].中国临床康复,2006,10(4):116-118,封三.DOI: 10.3321/j.issn:1673-8225.2006.04.049.
    [21]
    闫伦, 李辉超, 王大雷, 等. 咪喹莫特抑制兔耳瘢痕增生的机制研究[J]. 现代生物医学进展, 2013,13(7):1214-1218. DOI: 10.13241/j.cnki.pmb.2013.07.009.
    [22]
    何香,李洁,刘佳琦,等.自噬相关基因在博来霉素诱导小鼠皮肤纤维化中的表达及作用[J].中华烧伤杂志,2020,36(5):346-356.DOI: 10.3760/cma.j.cn501120-20200210-00047.
    [23]
    ElmelegyNG,HegazyAM,SadakaMS,et al.Electrophotobiomodulation in the treatment of facial post-burn hypertrophic scars in pediatric patients[J].Ann Burns Fire Disasters,2018,31(2):127-132.
    [24]
    AtiyehB, IbrahimA. Nonsurgical management of hypertrophic scars: evidence-based therapies, standard practices, and emerging methods: an update[J]. Aesthetic Plast Surg, 2020,44(4):1345-1347. DOI: 10.1007/s00266-020-01766-3.
    [25]
    ZhangH,WangHY,WangDL,et al.Effect of pressure therapy for treatment of hypertrophic scar[J].Medicine (Baltimore),2019,98(26):e16263.DOI: 10.1097/MD.0000000000016263.
    [26]
    Amini-NikS, YousufY, JeschkeMG. Scar management in burn injuries using drug delivery and molecular signaling: Current treatments and future directions[J]. Adv Drug Deliv Rev, 2018,123: 135-154. DOI: 10.1016/j.addr.2017.07.017.
    [27]
    LiJ,LiY,WangYC,et al.Overexpression of miR-101 suppresses collagen synthesis by targeting EZH2 in hypertrophic scar fibroblasts[J/OL].Burns Trauma,2021,9:tkab038[2021-12-13]. https://pubmed.ncbi.nlm.nih.gov/34859108/. DOI: 10.1093/burnst/tkab038.
    [28]
    DengXW, ChenQ, QiangLJ, et al. Development of a porcine full-thickness burn hypertrophic scar model and investigation of the effects of shikonin on hypertrophic scar remediation[J]. Front Pharmacol, 2018,9: 590. DOI: 10.3389/fphar.2018.00590.
    [29]
    赵文鲁积雪草甙对兔耳瘢痕模型TGF-β1基因表达的影响青岛青岛大学2009

    赵文鲁. 积雪草甙对兔耳瘢痕模型TGF-β1基因表达的影响[D]. 青岛:青岛大学, 2009.

    [30]
    BermanB,MaderalA,RaphaelB.Keloids and hypertrophic scars: pathophysiology, classification, and treatment[J].Dermatol Surg,2017,43 Suppl 1:S3-18.DOI: 10.1097/DSS.0000000000000819.
    [31]
    HarnHI, OgawaR, HsuCK, et al. The tension biology of wound healing[J]. Exp Dermatol, 2019,28(4):464-471. DOI: 10.1111/exd.13460.
    [32]
    JimiS, SaparovA, KoizumiS, et al. A novel mouse wound model for scar tissue formation in abdominal muscle wall[J]. J Vet Med Sci, 2021,83(12): 1933-1942. DOI: 10.1292/jvms.21-0464.
    [33]
    赵倩楠, 周粤闽, 孙朝阳. 机械张力对创伤后增生性瘢痕形成的影响研究进展[J]. 中华烧伤杂志, 2021,37(6): 586-590. DOI: 10.3760/cma.j.cn501120-20200315-00167.
    [34]
    ZhouQD, GongJX, BiJN, et al. KGF-2 regulates STAP-2-mediated signal transducer and activator of transcription 3 signaling and reduces skin scar formation[J]. J Invest Dermatol, 2022,142(7): 2003-2013.e5. DOI: 10.1016/j.jid.2021.12.018.
    [35]
    SeoCH, CuiHS, KimJB. Calpastatin-mediated inhibition of calpain ameliorates skin scar formation after burn injury[J]. Int J Mol Sci, 2021,22(11): 5771. DOI: 10.3390/ijms22115771.
    [36]
    TianS, ZhengYJ, XiaoSC, et al. Ivermectin inhibits cell proliferation and the expression levels of type I collagen, α-SMA and CCN2 in hypertrophic scar fibroblasts[J]. Mol Med Rep, 2021,24(1): 488. DOI: 10.3892/mmr.2021.12127.
    [37]
    HsiehSC, WuCC, HsuSL, et al. Gallic acid attenuates TGF-β1-stimulated collagen gel contraction via suppression of RhoA/Rho-kinase pathway in hypertrophic scar fibroblasts[J]. Life Sci, 2016,161:19-26. DOI: 10.1016/j.lfs.2016.07.011.
    [38]
    HwangboC, TaeN, LeeS, et al. Syntenin regulates TGF-β1-induced Smad activation and the epithelial-to-mesenchymal transition by inhibiting caveolin-mediated TGF-β type I receptor internalization[J]. Oncogene, 2016,35(3): 389-401. DOI: 10.1038/onc.2015.100.
    [39]
    RippaAL, KalabushevaEP, VorotelyakEA. Regeneration of dermis: scarring and cells involved[J]. Cells, 2019,8(6):607. DOI: 10.3390/cells8060607.
    [40]
    ZhengZ, ZhangXL, DangC, et al. Fibromodulin is essential for fetal-type scarless cutaneous wound healing[J]. Am J Pathol, 2016,186(11): 2824-2832. DOI: 10.1016/j.ajpath.2016.07.023.
    [41]
    HuangD,LiuYP,HuangYJ,et al.Mechanical compression upregulates MMP9 through SMAD3 but not SMAD2 modulation in hypertrophic scar fibroblasts[J].Connect Tissue Res,2014,55(5/6):391-396.DOI: 10.3109/03008207.2014.959118.
    [42]
    WangXX, GuC, ShangF, et al. Inhibitory effect of the LY2109761 on the development of human keloid fibroblasts[J]. Anal Cell Pathol (Amst), 2021,2021:8883427. DOI: 10.1155/2021/8883427.
    [43]
    周孝亮, 刘德伍, 毛远桂, 等. 粉防己碱对兔耳瘢痕增生组织Ⅰ、Ⅲ型胶原与TGF-β1基因表达的影响[J]. 中华整形外科杂志, 2013,29(6):406-412. DOI: 10.3760/cma.j.issn.1009-4598.2013.06.002.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(5)  / Tables(1)

    Article Metrics

    Article views (576) PDF downloads(48) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return