Identification Of Key Driver Genes In Keloid And Effect Of DKK3 On Keloid

Background Keloid impairs patients’ quality of life severely.Although many therapeutic strategies have been developed,most remain unsatisfactory with high recurrence,because of limited understanding of the mechanisms underlying keloid development.Thus,precise treatment is not possible.Methods Microarray was applied to detect gene expression profile of fibroblast and keratinocyte between keloid and normal skin.Weighted Gene Co-expression Network Analysis was applied to generate holistic views of gene network in fibroblast and keratinocyte with differentially expressed genes.Related gene modules and hub genes were identified and checked whether they were biologically related to keloid.DKK3,one hub gene,was selected to determine its effect on keloid with apoptosis detection,weight loss,Masson staining and Sirius red staining.Direct protein-protein interaction of DKK3 was predicted with HAPPI,Bio GRID,Inact and IPA.Results There are 2579 and 2553 differentially expressed genes were identified for fibroblast and keratinocyte respectively.And Weighted Gene Co-expression Network Analysis generated both three gene modules for fibroblast and keratinocyte.Blue modules were identified as the most related modules for fibroblast and keratinocyte and hub genes were also determined.Application of recombinant human DKK-3 protein induce fibroblast apoptosis and keloid tissue losing weight.Collagen deposit was also inhibited and the ration of collagen type I to collagen type III was rebalanced to some extent.Direct interacting proteins of DKK3 were predicted.Conclusion The present study provides a holistic view of gene networks of fibroblast and keratinocyte in keloid.Identified modules and hub genes are biologically related to keloid.DKK3,one hub gene,could inhibit keloid.Novel therapy based on mechanism of DKK3 function is promising.