Skin and hair follicle integrity is crucially dependent on β1 integrin expression on keratinocytes
Skin and hair follicle integrity is crucially dependent on β1 integrin expression on keratinocytes
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DOI：
10.1093/emboj/19.15.3990
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发表时间：
2000-08-01
期刊：
影响因子：
11.4
通讯作者：
Fässler, R
中科院分区：
文献类型：
--
作者：
Brakebusch, C;Grose, R;Fässler, R
β1整合素是广泛表达的受体，介导细胞与细胞、细胞与细胞外基质的相互作用。为了分析β1整合素在皮肤中的功能，我们使用cre-loxP系统产生了角质形成细胞限制性缺失β1整合素基因的小鼠。由于毛发基质细胞增殖减少和毛囊严重异常，突变小鼠出现了严重的脱发。最终，畸形的毛囊通过渗透巨噬细胞被移除。背部皮肤表皮增厚，基底层角质形成细胞α6β4整合素表达减少，半桥粒数减少。基底膜成分不典型地沉积，至少在层粘连蛋白-5的情况下，加工不当，导致基底膜破裂，真皮-表皮交界处形成水泡。相反，β1缺陷毛囊周围基底膜的完整性没有受到影响。最后，真皮变得纤维化。这些结果表明，β1整合素在毛囊形态发生、基底膜成分的加工、部分而非全部基底膜的维持、角质形成细胞的分化和增殖以及半桥粒的形成和/或维持中发挥重要作用。
beta 1 integrins are ubiquitously expressed receptors that mediate cell-cell and cell-extracellular matrix interactions. To analyze the function of beta 1 integrin in skin we generated mice with a keratinocyte-restricted deletion of the beta 1 integrin gene using the cre-loxP system. Mutant mice developed severe hair loss due to a reduced proliferation of hair matrix cells and severe hair follicle abnormalities. Eventually, the malformed hair follicles were removed by infiltrating macrophages. The epidermis of the back skin became hyperthickened, the basal keratinocytes showed reduced expression of alpha 6 beta 4 integrin, and the number of hemidesmosomes decreased. Basement membrane components were atypically deposited and, at least in the case of laminin-5, improperly processed, leading to disruption of the basement membrane and blister formation at the dermal-epidermal junction. In contrast, the integrity of the basement membrane surrounding the beta 1-deficient hair follicle was not affected. Finally, the dermis became fibrotic. These results demonstrate an important role of beta 1 integrins in hair follicle morphogenesis, in the processing of basement membrane components, in the maintenance of some, but not all basement membranes, in keratinocyte differentiation and proliferation, and in the formation and/or maintenance of hemidesmosomes.