Defective integrin alpha 6 beta 4 expression in the skin of patients with junctional epidermolysis bullosa and pyloric atresia
Defective integrin alpha 6 beta 4 expression in the skin of patients with junctional epidermolysis bullosa and pyloric atresia
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DOI：
10.1111/1523-1747.ep12363370
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发表时间：
1996-09-01
影响因子：
6.5
通讯作者：
Carter, WG
中科院分区：
文献类型：
--
作者：
Brown, TA;Gil, SG;Carter, WG
大疱性结缔组织表皮松解症（JEB）是一种异质性的罕见遗传性皮肤病，其中细胞粘附成分的缺陷导致半脂粒的不完全形成。我们使用针对整合素粘附受体α 3 β 1和α 6 β 4的单克隆抗体，以及针对基膜配体层粘连蛋白5的α 3、β 3和γ 2亚基的单克隆抗体，对10例JEB患者的皮肤进行了免疫组织化学检查（JEB重症，n = 4； JEB炎，n = 3； JEB合并幽门闭锁[JEB/PA]， n = 3）。与我们之前的报道一致，只有没有相关性幽门闭锁的JEB患者在表皮基底膜上表达了层粘连蛋白-5亚基的减少或缺失的表位。相比之下，所有3例JEB/PA患者在基底表皮细胞中均表现出整合素α 6 β 4的异常表达，但在层粘连蛋白5的表达中没有异常，使用5种识别细胞内和细胞外表位的不同单克隆抗体在JEB/PA患者的表皮活检中未检测到整合素β 4亚基。组织提取物的Western blot分析证实JEB/PA标本表皮中没有β 4亚基，JEB/PA患者表皮中整合素α 6亚基的表达是不同的。整合素α 6 β 4异常表达图谱定义了JEB合并幽门闭锁的亚群。这些结果强烈暗示了α 6 β 4在体内完整半粒粒的形成和基底角化细胞与基底膜的稳定粘附中的功能作用。
Junctional epidermolysis bullosa (JEB) is a heterogeneous group of rare inherited skin disorders in which defects in cell adhesion components cause incomplete formation of hemidesmosomes. We have immunohistochemically examined the skin from ten JEB patients (JEB gravis, n = 4; JEB mitis, n = 3; JEB plus pyloric atresia [JEB/PA], n = 3) using monoclonal antibodies specific for the integrin adhesion receptors alpha 3 beta 1 and alpha 6 beta 4, and for the alpha 3, beta 3, and gamma 2 subunits of the basement membrane ligand, laminin 5. Consistent with our previous reports, only the JEB gravis patients without associated pyloric atresia expressed reduced or absent epitopes for laminin-5 subunits in their epidermal basement membrane. In contrast, all three JEB/PA cases showed abnormalities in integrin alpha 6 beta 4, but not in Laminin 5, expression in their basal epidermal cells, Integrin beta 4 subunit was undetectable in the biopsied epidermis of these JEB/PA individuals using five different monoclonal antibodies that recognize both intra- and extracellular epitopes. The absence of the beta 4 subunit in the epidermis of JEB/PA specimens was confirmed by Western blot analysis of tissue extracts, Epidermal expression of the integrin alpha 6 subunit was variable in the JEB/PA patients. Abnormal integrin alpha 6 beta 4 expression map define the subset of JEB cases with pyloric atresia. These results strongly implicate a functional role for alpha 6 beta 4 in the formation of complete hemidesmosomes and in stable adhesion of basal keratinocytes to the basement membrane in vivo.