Targeting connexin43 expression accelerates the rate of wound repair

被引:239
|
作者
Qiu, C
Coutinho, P
Frank, S
Franke, S
Law, LY
Martin, P
Green, CR
Becker, DL
机构
[1] UCL, Dept Anat & Dev Biol, London WC1E 6BT, England
[2] Univ Auckland, Div Anat & Radiol, Auckland, New Zealand
关键词
D O I
10.1016/j.cub.2003.09.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The repair of tissue damage is a key survival process in all organisms and involves the coordinated activation of several cell types. Cell-cell communication is clearly fundamental to this process, and a great deal is known about extracellular communication within the wound site via cytokines [1, 2]. Here we show that direct cell-cell communication through connexin 43 (Cx43) gap junction channels [3, 4] also plays a major role in the wound healing process. In two different wound healing models, incisional and excisional skin lesions, we show that a single topical application of Cx43 antisense gel brings about a transient downregulation of Cx43 protein levels, and this results in a dramatic increase in the rate of wound closure. Cx43 knockdown reduces inflammation, seen both macroscopically, as a reduction in swelling, redness, and wound gape, and microscopically, as a significant decrease in neutrophil numbers in the tissue around the wound. One long-term consequence of the improved rate of healing is a significant reduction in the extent of granulation tissue deposition and the subsequent formation of a smaller, less distorted, scar. This approach is likely to have widespread therapeutic applications in other injured tissues and opens up new avenues of research into improving the wound healing process.
引用
收藏
页码:1697 / 1703
页数:7
相关论文
共 50 条
  • [31] Connexin43 Modulates Endothelial Wound Healing, Cell Proliferation and Locomotion
    Chen, Cheng-Hung
    Mayo, Jamie N.
    Bearden, Shawn E.
    FASEB JOURNAL, 2013, 27
  • [32] Connexin43, E-Cadherin, β-Catenin and ZO-1 Expression, and Aberrant Methylation of the Connexin43 Gene in NSCLC
    Jinn, Yasuto
    Inase, Naohiko
    ANTICANCER RESEARCH, 2010, 30 (06) : 2271 - 2278
  • [33] Connexin43 and ischemic preconditioning
    Schulz, Rainer
    Heusch, Gerd
    CARDIOVASCULAR GAP JUNCTIONS, 2006, 42 : 213 - 227
  • [34] Expression of connexin31 and connexin43 genes in early rat embryos
    Reuss, B
    Hellmann, P
    Traub, O
    Butterweck, A
    Winterhager, E
    DEVELOPMENTAL GENETICS, 1997, 21 (01): : 82 - 90
  • [35] Connexin43 Is Dispensable for Phagocytosis
    Glass, Aaron M.
    Wolf, Benjamin J.
    Schneider, Karin M.
    Princiotta, Michael F.
    Taffet, Steven M.
    JOURNAL OF IMMUNOLOGY, 2013, 190 (09): : 4830 - 4835
  • [36] Intramolecular interactions in connexin43: A structural basis for pH-dependent connexin43 gating
    Duffy, HS
    Sorgen, P
    Girvin, M
    Delmar, M
    Spray, DC
    CIRCULATION, 2001, 104 (17) : 310 - 310
  • [37] Connexin 43 Antisense Therapy Modulates Connexin Expression and Wound Repair in Nitrogen Mustard Injured Mouse Skin
    Chang, Yoke-chen
    Chang, Hui-Ying
    Hahn, Rita
    Lee, Esther
    Svoboda, Kathy
    Gordon, Marion
    Gerecke, Donald
    FASEB JOURNAL, 2015, 29
  • [38] Regulation of vascular connexin43 gene expression by mechanical loads
    Cowan, DB
    Lye, SJ
    Langille, BL
    CIRCULATION RESEARCH, 1998, 82 (07) : 786 - 793
  • [39] Targeting connexin hemichannels to control the inflammasome: the correlation between connexin43 and NLRP3 expression in chronic eye disease
    Mugisho, Odunayo O.
    Rupenthal, Ilva D.
    Paquet-Durand, Francois
    Acosta, Monica L.
    Green, Colin R.
    EXPERT OPINION ON THERAPEUTIC TARGETS, 2019, 23 (10) : 855 - 863
  • [40] Expression of Connexin43 in Cerebral Arteries of Patients with Moyamoya Disease
    Liao, Jiaqi
    Hong, Tao
    Xu, Jinxian
    Zeng, Erming
    Tang, Bin
    Lai, Wentao
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES, 2018, 27 (04): : 1107 - 1114