Email Alerts
RSS
Volume 39 Issue 12
Dec.  2023
Turn off MathJax
Article Contents
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2023  >  39(12): 1168-1174
Zhang QY,Zhang LX,Han DH,et al.Expression of endosialin in human hypertrophic scars and its regulation on fibroblast phenotype[J].Chin J Burns Wounds,2023,39(12):1168-1174.DOI: 10.3760/cma.j.cn501225-20231030-00154.
Citation: Zhang QY,Zhang LX,Han DH,et al.Expression of endosialin in human hypertrophic scars and its regulation on fibroblast phenotype[J].Chin J Burns Wounds,2023,39(12):1168-1174.DOI: 10.3760/cma.j.cn501225-20231030-00154.
shu

Expression of endosialin in human hypertrophic scars and its regulation on fibroblast phenotype

doi: 10.3760/cma.j.cn501225-20231030-00154
  • 1.

    Department of Burns and Cutaneous Surgery, Burn Center of PLA, the First Affiliated Hospital of Air Force Medical University, Xi'an 710032, China

  • 2.

    The Third Student Battalion, School of Basic Medical Sciences of Air Force Medical University, Xi'an 710032, China

  • 3.

    Department of Urology, the First Affiliated Hospital of Air Force Medical University, Xi'an 710032, China

Funds:

Youth Science Foundation Program of National Natural Science Foundation of China 81501666, 82302809

Shaanxi Provincial Key Research and Development Plan 2022SF-399

More Information
  • Corresponding author: Yang Yunshu, Email: yangys0815@qq.com
  • Received Date: 2023-10-30
    Abstract
  •   Objective   To explore the expression of endosialin, i.e., CD248 in human hypertrophic scars (HSs) and its regulatory effect on the phenotype of hypertrophic scar fibroblasts (HSFs).   Methods   The method of experimental research was used. From March to May, 2023, 3 pediatric patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 2 females and 1 male, aged one year ten months to two years. The HS tissue resected during the surgery and the remaining full-thickness skin graft, i.e., normal skin tissue after full-thickness skin grafting were collected from the aforementioned pediatric patients for subsequent experiments. Using the aforementioned two types of tissue, the histological structures were observed by hematoxylin-eosin staining, collagen distribution was observed by Masson staining, and the expression of CD248 was observed and measured by immunohistochemical staining. The primary HSFs were isolated from HS tissue using explant culture technique, and the 3 rd to 5 th passages of HSFs were used in subsequent experiments. According to the random number table, HSFs were divided into immunoglobulin G78 (IgG78)-treated group and IgG control group, which were treated with 200 nmol/L human CD248 monoclonal antibody IgG78 and human IgG control antibody for 24 h, respectively. The mRNA expressions of collagen type Ⅰ (Col Ⅰ) and α-smooth muscle actin (α-SMA) in HSFs were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction, the protein expressions of Col Ⅰ and α-SMA in HSFs were detected by Western blotting, and the intracellular location and protein expressions of Col Ⅰ and α-SMA were detected by immunofluorescence method. The number of samples in each experiment was 3. Data were statistically analyzed with paired sample t test and independent sample t test.   Results   Compared with those in normal skin tissue, the epidermis and dermis in HS tissue were significantly thicker, with massive accumulation and disordered arrangement of collagen in the dermis. The expression of CD248 in HS tissue was significantly upregulated compared with that in normal skin tissue ( t=5.29, P<0.05). At post treatment hour 24, the mRNA expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were 0.39±0.05 and 0.56±0.09, respectively, which were significantly lower than 1.00±0.07 and 1.00±0.08 in IgG control group, respectively (with t values of 11.87 and 6.49, respectively, P values all <0.05). The protein expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were 0.617±0.011 and 0.67±0.14, respectively, which were significantly lower than 1.259±0.052 and 1.23±0.16 in IgG control group, respectively (with t values of 20.92 and 4.52, respectively, P values all <0.05). At post treatment hour 24, immunofluorescence staining showed that Col Ⅰ and α-SMA mainly located in the cytoplasm of HSFs in the two groups, and the protein expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were obviously downregulated compared with those in IgG control group.   Conclusions   The expression of CD248 is significantly upregulated in human HS. Targeted blockade of CD248 can significantly inhibit the collagen synthesis by HSFs and the transdifferentiation of HSFs into myofibroblasts.

     

    • FullText(HTML)
  • loading
    • References(31)
  • [1]
    史亮亮,刘名倬,江政英,等.药物干预增生性瘢痕的研究进展[J].中华烧伤与创面修复杂志,2022,38(12):1179-1184.DOI: 10.3760/cma.j.cn501120-20211118-00388.
    [2]
    FinnertyCC,JeschkeMG,BranskiLK,et al.Hypertrophic scarring: the greatest unmet challenge after burn injury[J].Lancet,2016,388(10052):1427-1436.DOI: 10.1016/S0140-6736(16)31406-4.
    [3]
    KarppinenSM,HeljasvaaraR,GullbergD,et al.Toward understanding scarless skin wound healing and pathological scarring[J].F1000Res,2019,8:F1000 Faculty Rev-787.DOI: 10.12688/f1000research.18293.1.
    [4]
    FinlayV,BurrowsS,KendellR,et al.Modified Vancouver Scar Scale score is linked with quality of life after burn[J].Burns,2017,43(4):741-746.DOI: 10.1016/j.burns.2016.11.007.
    [5]
    OgawaR.The most current algorithms for the treatment and prevention of hypertrophic scars and keloids: a 2020 update of the algorithms published 10 years ago[J].Plast Reconstr Surg,2022,149(1):79e-94e.DOI: 10.1097/PRS.0000000000008667.
    [6]
    SchulzJN,PlomannM,SengleG,et al.New developments on skin fibrosis-essential signals emanating from the extracellular matrix for the control of myofibroblasts[J].Matrix Biol,2018,68-69:522-532.DOI: 10.1016/j.matbio.2018.01.025.
    [7]
    WalravenM,HinzB.Therapeutic approaches to control tissue repair and fibrosis: extracellular matrix as a game changer[J].Matrix Biol,2018,71-72:205-224.DOI: 10.1016/j.matbio.2018.02.020.
    [8]
    ŢuţuianuR,RoşcaAM,FloreaG,et al.Heterogeneity of human fibroblasts isolated from hypertrophic scar[J].Rom J Morphol Embryol,2019,60(3):793-802.
    [9]
    RodriguesM,KosaricN,BonhamCA,et al.Wound healing: a cellular perspective[J].Physiol Rev,2019,99(1):665-706.DOI: 10.1152/physrev.00067.2017.
    [10]
    ShirakamiE,YamakawaS,HayashidaK.Strategies to prevent hypertrophic scar formation: a review of therapeutic interventions based on molecular evidence[J/OL].Burns Trauma,2020,8:tkz003[2023-10-30].https://pubmed.ncbi.nlm.nih.gov/32341924/.DOI: 10.1093/burnst/tkz003.
    [11]
    KhanKA,NaylorAJ,KhanA,et al.Multimerin-2 is a ligand for group 14 family C-type lectins CLEC14A, CD93 and CD248 spanning the endothelial pericyte interface[J].Oncogene,2017,36(44):6097-6108.DOI: 10.1038/onc.2017.214.
    [12]
    ValdezY,MaiaM,ConwayEM.CD248: reviewing its role in health and disease[J].Curr Drug Targets,2012,13(3):432-439.DOI: 10.2174/138945012799424615.
    [13]
    Di BenedettoP,RuscittiP,LiakouliV,et al.Linking myofibroblast generation and microvascular alteration: the role of CD248 from pathogenesis to therapeutic target (review)[J].Mol Med Rep,2019,20(2):1488-1498.DOI: 10.3892/mmr.2019.10429.
    [14]
    ChristianS,AhornH,KoehlerA,et al.Molecular cloning and characterization of endosialin, a C-type lectin-like cell surface receptor of tumor endothelium[J].J Biol Chem,2001,276(10):7408-7414.DOI: 10.1074/jbc.M009604200.
    [15]
    LiuS,HanD,XuC,et al.Antibody-drug conjugates targeting CD248 inhibits liver fibrosis through specific killing on myofibroblasts[J].Mol Med,2022,28(1):37.DOI: 10.1186/s10020-022-00460-1.
    [16]
    XuC,LiuS,YangF,et al.Antibody-drug conjugates targeting CD248+ myofibroblasts effectively alleviate renal fibrosis in mice[J].FASEB J,2022,36(2):e22102.DOI: 10.1096/fj.202101441R.
    [17]
    ZhangJ,LiY,BaiX,et al.Recent advances in hypertrophic scar[J].Histol Histopathol,2018,33(1):27-39.DOI: 10.14670/HH-11-908.
    [18]
    MarzecM,Kandefer-GolaM,JanusI,et al.Endosialin (CD248) expression in fibromas and soft-tissue fibrosarcomas in dogs[J].In Vivo,2021,35(3):1467-1472.DOI: 10.21873/invivo.12399.
    [19]
    XuC,ZhangK,YangF,et al.CD248+ cancer-associated fibroblasts: a novel prognostic and therapeutic target for renal cell carcinoma[J].Front Oncol,2021,11:773063.DOI: 10.3389/fonc.2021.773063.
    [20]
    PaiCH,LinSR,LiuCH,et al.Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis[J].Sci Rep,2020,10(1):16772.DOI: 10.1038/s41598-020-73194-x.
    [21]
    MatsushimaS,AoshimaY,AkamatsuT,et al.CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes[J].BMC Pulm Med,2020,20(1):21.DOI: 10.1186/s12890-020-1054-9.
    [22]
    CiprianiP,RuscittiP,Di ColaI,et al.Fibroblast expression of CD248 may contribute to exacerbation of microvascular damage during systemic sclerosis[J].Rheumatology (Oxford),2023,62(3):1317-1325.DOI: 10.1093/rheumatology/keac377.
    [23]
    Di BenedettoP,LiakouliV,RuscittiP,et al.Blocking CD248 molecules in perivascular stromal cells of patients with systemic sclerosis strongly inhibits their differentiation toward myofibroblasts and proliferation: a new potential target for antifibrotic therapy[J]. Arthritis Res Ther,2018,20(1):223.DOI: 10.1186/s13075-018-1719-4.
    [24]
    BartisD,CrowleyLE,D'SouzaVK,et al.Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis[J].BMC Pulm Med,2016,16(1):51.DOI: 10.1186/s12890-016-0211-7.
    [25]
    WilhelmA,AldridgeV,HaldarD,et al.CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism[J].Gut,2016,65(7):1175-1185.DOI: 10.1136/gutjnl-2014-308325.
    [26]
    KuoCH,WuYF,ChangBI,et al.Interference in melanoma CD248 function reduces vascular mimicry and metastasis[J].J Biomed Sci,2022,29(1):98.DOI: 10.1186/s12929-022-00882-3.
    [27]
    WuJ,LiuX,WuJ,et al.CXCL12 derived from CD248-expressing cancer-associated fibroblasts mediates M2-polarized macrophages to promote nonsmall cell lung cancer progression[J].Biochim Biophys Acta Mol Basis Dis,2022,1868(11):166521.DOI: 10.1016/j.bbadis.2022.166521.
    [28]
    MoglerC,WielandM,KönigC,et al.Hepatic stellate cell-expressed endosialin balances fibrogenesis and hepatocyte proliferation during liver damage[J].EMBO Mol Med,2015,7(3):332-338.DOI: 10.15252/emmm.201404246.
    [29]
    ArmulikA,GenovéG,BetsholtzC.Pericytes: developmental, physiological, and pathological perspectives, problems, and promises[J].Dev Cell,2011,21(2):193-215.DOI: 10.1016/j.devcel.2011.07.001.
    [30]
    WangZ,SongQ,LiH.Suppressive effects of human fetal keratinocytes on the proliferation, differentiation and extracellular matrix synthesis of human hypertrophic scar fibroblasts in vitro[J].Mol Med Rep,2017,16(4):5377-5385.DOI: 10.3892/mmr.2017.7220.
    [31]
    周祥,杨发,韩东晖,等.CD248抗体IgG78抑制HFL-1人胚肺成纤维细胞的增殖、迁移[J].细胞与分子免疫学杂志,2021,37(4):289-294.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 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(4)  / Tables(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (817) PDF downloads(19) Cited by()
    Proportional views
    Related

    Copyright © Chinese Journal of Burns京ICP备07035254号-14

    E-mail：shaoshangzazhi@163.com

    Website：https://zhsszz.xml-journal.net/

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return