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

doi:10.3969/j.issn.2095-4344.2014.29.005

Abstract

Abstract:

BACKGROUND: The development of keloid is a progress of fibrosis in wound healing, and involves various fibrosis-related cytokines. Bone morphogenetic protein 7 (BMP7), 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 investigate the 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.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words:

keloid, bone morphogenetic protein 7, vascular endothelial growth factors, high mobility group proteins

CLC Number:

R318

Liu Yu-fang, Lin Mao, Hou Bin-bin, Hou Na, Liu Xia, Wang Dan, Xu Xue-zhu. Expression of bone morphogenetic protein 7, Gremlin, vascular endothelial growth factor and high mobility group box-1 in keloid and normal skin[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(29): 4618-4624.

Figures/Tables 2

2.1 两组标本基础资料比较见表1。 2.2 免疫组织化学检测结果显微镜下观察胞核或胞质中出现棕色或棕黄色颗粒为阳性细胞，未着色者为阴性细胞。可见骨形态发生蛋白7在正常皮肤组织中从表皮到真皮各层广泛着色，呈强阳性表达(图1A)。而在大部分瘢痕疙瘩组织中呈阴性表达(图1B)。由表1可见，骨形态发生蛋白7蛋白在正常皮肤组织与瘢痕疙瘩组织中的阳性表达率为95%，10%，差异有显著性意义(P < 0.01)。 Gremlin、高迁移率族蛋白B1及血管内皮生长因子在瘢痕疙瘩组织中均呈阳性表达，在大部分正常皮肤中均呈阴性表达。Gremlin主要表达于瘢痕疙瘩表皮基底层细胞、成纤维细胞及血管内皮细胞胞浆中(图1C，D)。高迁移率族蛋白B1主要表达于瘢痕疙瘩表皮基底层细胞及血管内皮细胞胞质中(图2)。血管内皮生长因子主要表达于表皮基底层及棘层细胞、血管内皮细胞胞浆中(图3)。 2.3 四种细胞因子在正常皮肤和瘢痕疙瘩组织中的阳性表达率见表2。由表2可见Gremlin在正常皮肤组织及瘢痕疙瘩组织中的阳性表达率分别为5%和40%，差异有显著性意义(P < 0.01)。高迁移率族蛋白B1在正常皮肤组织及瘢痕疙瘩组织中的阳性表达率分别为25%和70%，差异有显著性意义(P < 0.01)。血管内皮生长因子在正常皮肤组织及瘢痕疙瘩组织中的阳性表达率分别为20%和90%。差异有显著性意义(P < 0.01)。 2.4 瘢痕疙瘩组织中骨形态发生蛋白7与Gremlin、高迁移率族蛋白B1与血管内皮生长因子表达的相关关系见表3，表4。经Spearman关联性分析，在瘢痕疙瘩组织中骨形态发生蛋白7与Gremlin的表达呈显著的负相关，差异有显著性意义(r=-0.539，P < 0.05)。高迁移率族蛋白B1与血管内皮生长因子在瘢痕疙瘩组织中的表达呈明显的正相关，差异有显著性意义(r=0.560，P < 0.05)。 2.5 Western检测结果在蛋白水平上，由图4可见，骨形态发生蛋白7在正常皮肤组织中呈高表达，在瘢痕疙瘩组织中表达明显减少，两组相比骨形态发生蛋白7蛋白的相对表达量差异有显著性意义(P < 0.05)。Gremlin、高迁移率族蛋白B1与血管内皮生长因子在瘢痕疙瘩中表达明显增高，在正常皮肤中低表达，两组相比差异有显著性意义(P < 0.05)。"

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