Karelina T V, Bannikov G A, Eisen A Z
Division of Dermatology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Invest Dermatol. 2000 Feb;114(2):371-5. doi: 10.1046/j.1523-1747.2000.00886.x.
Epithelial cell adhesion, migration, and differentiation are controlled by interactions at the basement membrane zone (BMZ). Type VII collagen is the major collagenous component of anchoring fibrils that are essential for the attachment of the epidermis to the dermis. Gelatinase A (MMP-2) is believed to be necessary for the degradation of type VII collagen. In this study we have examined the in vivo distribution of type VII collagen and gelatinase A (Gel A) in the developing human epidermis and its appendages. At 13-15 wk of gestation a marked decrease in type VII collagen immunoreactivity was seen in the BMZ surrounding invading appendageal buds; however, type VII collagen mRNA was strongly expressed in the budding epidermal keratinocytes adjacent to the BMZ. At these stages, Gel A-positive mesenchymal-like cells were found scattered throughout the stroma with numerous Gel A-containing cells in direct contact with the developing appendageal buds. In situ zymography was used to show Gel A-activity in vivo. Gel A-mediated lysis was present at the interface between the appendageal buds and the underlying BMZ. By 20-25 wk of gestational age, immunostaining for type VII collagen protein was absent from the BMZ surrounding the distal portion of invading appendageal epithelial cords of both hair follicles and sweat glands. In contrast, type VII collagen mRNA was present in the basal keratinocytes adjacent to the BMZ surrounding the distal portion of these invading appendageal epithelial cords. At these stages Gel A-positive cells were present in the stroma directly adjacent to the distal portion of developing appendageal cords that lacked type VII collagen. In situ zymography showed zones of Gel A-mediated stromal lysis at the distal portion of developing appendageal cords. Interestingly, no differences were seen in the distribution of type IV collagen in the BMZ of both budding and resting fetal epidermis. These observations suggest that the absence of type VII collagen protein correlates directly with the presence of Gel A-activity at the BMZ. Gel A appears to play a major role in appendageal development and contributes to remodeling of the BMZ during fetal skin morphogenesis.
上皮细胞的黏附、迁移和分化受基底膜区（BMZ）的相互作用控制。Ⅶ型胶原蛋白是锚定纤维的主要胶原成分，对表皮与真皮的附着至关重要。明胶酶A（MMP - 2）被认为是降解Ⅶ型胶原蛋白所必需的。在本研究中，我们检测了Ⅶ型胶原蛋白和明胶酶A（Gel A）在发育中的人类表皮及其附属器中的体内分布。在妊娠13 - 15周时，在侵入的附属器芽周围的BMZ中观察到Ⅶ型胶原蛋白免疫反应性显著降低；然而，Ⅶ型胶原蛋白mRNA在与BMZ相邻的出芽表皮角质形成细胞中强烈表达。在这些阶段，发现Gel A阳性的间充质样细胞散在分布于整个基质中，有许多含Gel A的细胞与发育中的附属器芽直接接触。原位酶谱法用于显示体内Gel A活性。Gel A介导的裂解存在于附属器芽与下方BMZ的界面处。到妊娠20 - 25周时，毛囊和汗腺侵入的附属器上皮索远端周围的BMZ中，Ⅶ型胶原蛋白蛋白免疫染色缺失。相反，在这些侵入的附属器上皮索远端周围与BMZ相邻的基底角质形成细胞中存在Ⅶ型胶原蛋白mRNA。在这些阶段，Gel A阳性细胞存在于直接与缺乏Ⅶ型胶原蛋白的发育中的附属器索远端相邻的基质中。原位酶谱法显示在发育中的附属器索远端有Gel A介导的基质裂解区域。有趣的是，在出芽和静止的胎儿表皮的BMZ中，Ⅳ型胶原蛋白的分布没有差异。这些观察结果表明，Ⅶ型胶原蛋白蛋白的缺失与BMZ处Gel A活性的存在直接相关。Gel A似乎在附属器发育中起主要作用，并在胎儿皮肤形态发生过程中有助于BMZ的重塑。
