CCN1 Accelerates Re-epithelialization By Promoting Keratinocyte Migration And Proliferation During Cutaneous Wound Healing

Backgroud: Wounds are most common skin damage world-wide.During cutaneous wound healing,re-epithelialization is the essential process that have a great influence on the prognosis.Currently,CCN family member 1(CCN1 or Cysteine-rich 61,CYR61)has been reported to be effective in treating cutaneous wounds.However,its role in re-epithelialization still remains unclear.Objective: To investigate the expression and function of CCN1 in re-epithelialization.Methods: CCN1 expression were detected through microarray and immunofluorecence of wounded skin.The effect of CCN1 on migration and proliferation of human primary keratinocytes were studied by wound scratch assay,colloidal gold assay,Cell Titer-Glo assay and Ed U assay.Moreover,animal studies were conducted on a superfical second-degree burn mice model treated with CCN1 intracutaneously.For the assessment of wound healing,digital photographs were taken at 1,4,7,11 and 14 days.Animals were sacrificed at 1,4 and 14 days for histological examination.Results: Through microarray and immunofluorecence staining,we discovered that CCN1 is upregulated during the early stage of wound healing.The in vitro results showed that CCN1 treatment could promote keratinocyte migration and proliferation.In animal studies,topical treatment with CCN1 protein was shown to accelerate wound closure and re-epithelialization in mice models.Immunoluorescent analysis showed elevated expression of PCNA and Ki67 in CCN1 treated group compared with control group 4 days post-burn.Conclusion: CCN1 accelerates re-epithelialization by promoting keratinocytes migration and proliferation and might be a potential therapeutic target for non-healing wounds or burn wounds.