增生性瘢痕与瘢痕疙瘩上皮间质转化及CD26表达的异质性研究

Heterogeneity of epithelial-mesenchymal transition and CD26 expression in hypertrophic scars and keloids

目的通过对比分析增生性瘢痕、浅表扩张型瘢痕疙瘩的边缘和中心及正常皮肤E-cadherin、Vimentin、基质金属蛋白酶-9(matrix metalloprotein-9,MMP-9)、肿瘤坏死因子-α(tumor necrosis factor alpha,TNF-α)、二肽基肽酶-4(dipeptidyl-peptidase 4,DPP4,又称CD26)的表达以及组织学上的差异。方法纳入2020年10月至2021年8月本院整形烧伤外科行瘢痕疙瘩及增生性瘢痕切除手术患者各10例,收集其切除的瘢痕疙瘩及增生性瘢痕组织,另取需要进行部分正常皮肤切除手术的8例患者正常皮肤组织。HE染色观察各组织形态,免疫组化和Western blot检测E-cadherin、Vimentin、MMP-9、TNF-α、CD26在组织中的表达。结果免疫组化及Western blot检测结果显示瘢痕疙瘩和增生性瘢痕表皮层的E-cadherin表达均较正常皮肤明显减弱(P<0.05),瘢痕疙瘩边缘较中心明显减弱(P<0.05),增生性瘢痕边缘与中心无明显差异;瘢痕疙瘩和增生性瘢痕表皮层中的Vimentin、MMP-9、TNF-α、CD26表达较正常皮肤明显增强(P<0.05),瘢痕疙瘩边缘较中心明显增强(P<0.05),增生性瘢痕边缘与中心无明显差异。结论上皮间质转化(epithelium-to-mesenchymal transition,EMT)程度及在个体瘢痕内部的差异可能是增生性瘢痕与瘢痕疙瘩临床表现差异的原因之一,TNF-α及CD26可能是其中的关键因子。

Objective To investigate the histological differences and expression of E-cadherin,Vimentin,matrix metalloprotein-9(MMP-9),TNF-α,dipeptidyl-peptidase 4(DPP4,also called CD26)in the margin and center of hypertrophic scar,superficial dilated keloid and normal skin.Methods Ten patients with keloid and another 10 with hypertrophic scar undergoing excision surgery in our hospital from October 2020 to August 2021 were included,and 8 cases requiring partial normal skin resection were also recruited.The resected tissues were collected,the tissue morphology was observed with HE staining,and the expression levels of E-cadherin,Vimentin,MMP-9,TNF-αand CD26 were detected by immunohistochemical staining and Western blotting.Results The E-cadherin expression in the epidermis of both keloid and hypertrophic scar was significantly lower than that of normal skin(P<0.05),and the level in the edge of keloid was obviously weakened as compared with that of the center(P<0.05),but there was no significant difference between the edge of hypertrophic scar and the center(P>0.05).By contrast,the expression levels of Vimentin,MMP-9,TNF-αand CD26 in the epidermis of both keloid and hypertrophic scar were remarkably enhanced when compared with those of normal skin(P<0.05),and the keloids’edge higher than the center(P<0.05),while no significance between the hypertrophic scars’edge and center(P>0.05).Conclusion The differences in epithelial-to-mesenchymal transition(EMT)and expression of relevant biomarkers within individual scars may be one of the reasons for the diversity of clinical features between hypertrophic scar and keloid,in which TNF-αand CD26 may be the key factors.