瘢痕疙瘩中心与边缘表皮层形态学和上皮间质转化相关指标表达的异质性研究

Heterogeneity:epidermal morphology and expression of epithelial-mesenchymal transition-related factors between the center and margin of keloids

目的通过对比分析瘢痕疙瘩边缘、中心及正常皮肤E-cadherin、Vimentin、血管内皮生长因子(vascular endothelial growth factor,VEGF)和缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)表达以及表皮层组织学上的差异,探讨瘢痕疙瘩侵袭性生长的原因。方法纳入2019年10月至2020年8月本院整形烧伤外科行瘢痕疙瘩切除手术的患者16例,共16个瘢痕疙瘩组织,以及需要进行部分正常皮肤切除的手术患者9例,共9个正常皮肤组织,使用HE染色观察瘢痕疙瘩边缘、中心及正常皮肤组织形态,免疫组化染色和Western blot检测E-cadherin、Vimentin、VEGF和HIF-1α蛋白在不同组织中的表达。结果瘢痕疙瘩表皮层存在明显异常及异质性,边缘表皮层呈细分枝状并明显深入真皮,形成较深的犬牙交错状表现,而中心表皮层增厚扁平;免疫组化及Western blot检测结果均显示:瘢痕疙瘩边缘和中心表皮层E-cadherin表达显著低于正常皮肤(P<0.05),且边缘显著低于中心(P<0.05);Vimentin、HIF-1α、VEGF表达显著高于正常皮肤(P<0.05),边缘显著高于中心(P<0.05)。结论瘢痕疙瘩边缘表皮呈分枝状并明显向真皮层延伸,上皮间质转化活跃,HIF-1α及VEGF高表达且微血管丰富,可能与瘢痕疙瘩边缘的侵袭性生长相关,HIF-1α可能是其中的关键因子。

Objective To investigate the causes of keloid invasive growth by comparing the expressional differences of E-cadherin, vimentin, vascular endothelial growth factor(VEGF) and hypoxia-inducible factor-1(HIF-1α), and the epidermal histological differences among keloid marginal region, central region and normal skin. Methods This study enrolled 16 patients undergoing keloid resection in our department from October 2019 to August 2020, with a total of 16 keloid tissues, and 9 patients who required partial normal skin resection during the operation, with a total of 9 normal skin tissues. Hematoxylin and eosin(H&E) staining was used to observe the tissue morphology, and immunohistochemical staining and Western blot assay were used to detect the expression of E-cadherin, vimentin, VEGF and HIF-1α in above tissues. Results There was obvious abnormality and heterogeneity in the epidermal layer of keloids. The marginal epidermal subdivided into fine-branch-like and then clearly penetrated into the dermis, forming a houndstooth-like appearance, while the central epidermal became thick and flat;Immunohistochemical staining and Western blot assay showed that the expression level of E-cadherin was significantly weaker in the marginal and central epidermal of keloid tissue than in the normal skin(P<0.05), with that in the margin weaker than the center(P<0.05);The levels of vimentin, HIF-1α and VEGF were significantly higher in the keloid tissue than normal skin(P<0.05), and those in the margin took the highest(P<0.05). Conclusion Marginal epidermis of keloid clearly extends to the dermis in branched appearance, with active epithelium-to-mesenchymal transition(EMT), highly expressed HIF-1α, VEGF and abundant microvessels. The underlying mechanism may be related to the aggressive growth of the keloid edge, and HIF-1α might be the key factor.