瘢痕疙瘩及正常皮肤中骨形态发生蛋白7、Gremlin、血管内皮生长因子、高迁移率族蛋白B1的表达

Expression of bone morphogenetic protein 7, Gremlin, vascular endothelial growth factor and high mobility group box-1 in keloid and normal skin

背景:瘢痕疙瘩的发生是创伤修复的纤维化过程,多种纤维化相关细胞因子参与其发生发展。骨形态发生蛋白7、Gremlin与高迁移率族蛋白B1在其他器官纤维化中发挥重要作用,而在瘢痕疙瘩组织中的研究少见报道。目的:分析骨形态发生蛋白7、Gremlin(骨形成蛋白拮抗剂家族成员)、血管内皮生长因子与高迁移率族蛋白B1在瘢痕疙瘩发病机制中的作用和意义。方法:采用免疫组织化学方法及Wsetern Blot法检测骨形态发生蛋白7、Gremlin、血管内皮生长因子与高迁移率族蛋白B1在20例瘢痕疙瘩组织和20例正常皮肤组织中的分布及蛋白水平的表达,并对瘢痕疙瘩组织中骨形态发生蛋白7与Gremlin、血管内皮生长因子与高迁移率族蛋白B1的表达情况进行相关性分析。结果与结论:与正常皮肤组织相比,Gremlin、血管内皮生长因子与高迁移率族蛋白B1在瘢痕疙瘩组织中表达呈显著性上调(P<0.01),而骨形态发生蛋白7的表达呈显著性下调(P<0.01),Gremlin与骨形态发生蛋白7在瘢痕疙瘩中的表达呈显著性负相关(r=-0.539,P<0.05)。血管内皮生长因子与高迁移率族蛋白B1在瘢痕疙瘩中的表达呈显著性正相关(r=0.560,P<0.05)。说明Gremlin的过度表达和骨形态发生蛋白7的表达下调,以及高迁移率族蛋白B1与血管内皮生长因子的高表达可能共同参与了瘢痕疙瘩的纤维化病理过程。

BACKGROUND： The development of keloid is a progress of fibrosis in wound healing, and involves various fibrosis-related cytokines Bone morphogenetic protein 7 （BMPT）, Gremlin and high mobility group box-1 （HMGB1） play an important role in fibrosis of many organs, but their role in keloid tissue has rarely been reported. OBJECTIVE： To investigatethe role of BMP7, Gremlin, vascular endothelial growth factor （VEGF） and HMGB1 in the development of keloid. METHODS： The protein levels and distribution of BMP7, Gremlin, VEGF and HMGB1 in 20 cases of keloid and 20 cases of normal skin were detected by immunohistochemistry and western blot analysis, respectively. And the correlations among expression levels of BMP7, Gremlin, VEGF and HMGB1 in keloid were analyzed. RESULTS AND CONCLUSION＂ In keloid tissue, the expression levels of Gremlin, VEGF and HMGB1 were significantly higher than that in normal skin （P 〈 0.01 ）, while the expression levels of BMP7 were significantly lower （P 〈 0.01 ）. The levels of Gremlin were negatively correlated with the levels of BMP7 （r=-0.539, P 〈 0.05）. And the levels of VEGF were positively correlated with the levels of HMGB1 （r=0.56, P 〈 0.05）. The overexpression of Gremlin and decreased expression of BMP7, as well as the increased expression of HMGB1 and VEGF, may contribute to the pathogenesis of fibrosis in the development of keloid.