Study On The Heterogeneity Of Keloid Center And Marginal Epidermal Morphology And Expression Of Related Indexes Of Epithelium-to-mesenchymal Transition

Objective: Keloid is a benign fibroproliferative disease with unknown etiology.Due to its obvious internal heterogeneity,the margin is an invasive growth area,and the center is a relatively stable area.Therefore,more and more scholars hope to compare the center and edge of keloids.In order to find out the reasons for keloid tumor-like growth(invasive,recurrent),but in the past,it was mostly a comparative study of keloid dermis and fibroblasts,and there was a lack of research on the epidermis and keratinocytes.However,existing studies have shown that scar epidermis and stratum corneum have obvious abnormalities and participate in the aggressive growth of keloids through epithelium-to-mesenchymal transition(EMT).Therefore,this study intends to compare and analyze the keloid scar margin,center and normal skin E-cadherin,vimentin,Vascular Endothelial Growth Factor(VEGF),and HypoxiaInducible Factor-1α(HIF-1α)expression and epidermal histological differences,explore the reasons for the invasive growth of keloids,and provide new treatment ideas for clinically inhibiting scar growth and promoting its regression.Methods: This study included 16 patients who underwent keloid resection in the plastic surgery department of our hospital from October 2019 to August2020,and 9 patients who needed partial normal skin resection.A total of 16 keloid tissues and 9 normal skin tissues were collected.All tissues were divided into three groups,keloids Margin group,keloid center group and normal skin group,hematoxylin and eosin(H&E)staining were used to observe the morphological differences between the tissue groups,and immunofluorescence staining was used to detect E-cadherin,Vimentin co-expression in the three groups of tissues,immunohistochemical staining and western blot method to detect the expression of E-cadherin,Vimentin,VEGF and HIF-1α protein in the three tissues.Results: The epidermis of keloid is thicker than that of normal skin and has obvious heterogeneity.The marginal epidermis is subdivided into branches and goes deep into the dermis,forming a deep crisscross appearance.The central epidermis is thickened and flat.From the center to the margin,the branches of the epidermis become longer and thinner,and gradually deepen into the dermis.The morphology of keratinocytes in the basal layer and part of the spinous layer changes It is long fusiform with enlarged intercellular space,especially deep into the dermis。Immunofluorescence showed that E-cadherin and Vimentin co-expression existed in the epidermal layer of keloids,especially in the marginal basal layer.There was no obvious co-expression in the epidermal layer of normal skin.Immunohistochemistry showed that the expression of E-cadherin at the margin and center of keloids was significantly weaker than that of normal skin(P<0.05),and the margin was significantly weaker than the center(P<0.05).Vimentin expression was significantly stronger than that of normal skin(P<0.05),the margin was significantly stronger than the center(P<0.05).The expression of HIF-1α and VEGF in the epidermis and dermis of keloids was significantly higher than that of normal skin(P<0.05),and the margin was significantly higher than the center(P<0.05).WB test further proved that the expression of E-cadherin at the margin and center of keloids was significantly weaker than that of normal skin(P<0.05),and the margin was significantly weaker than the center(P<0.05).The expression of Vimentin,HIF-1α,and VEGF was significantly higher than that of normal skin(P<0.05).<0.05),the margin was significantly higher than the center(P<0.05).Conclusion: marginal epidermis of keloid was branched and clearly extends to the dermis,the epithelium-to-mesenchymal transition(EMT)was active,VEGF is highly expressed and the microvessels are abundant,which may be related to the aggressive growth of the keloid edge.HIF-1α may be the key factor.