Collagen IV in Normal Skin and in Pathological Processes.
Collagen IV in Normal Skin and in Pathological Processes.
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DOI：
10.4103/1947-2714.92892
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Howard MS
中科院分区：
文献类型：
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作者：
Abreu-Velez AM;Howard MS
IV型胶原蛋白是主要在基底膜区域内的皮肤中发现的一种胶原蛋白。IV型胶原蛋白C4结构域在C端的翻译后加工中不被去除，因此纤维头对头连接，而不是以平行方式连接。此外，IV型胶原蛋白在紧密胶原蛋白螺旋所必需的每三个氨基酸残基中缺乏甘氨酸。因此，相对于其他胶原亚型，整体胶原-IV构象在结构上更柔韧和扭结。这些结构特征允许胶原IV形成片层，这是在皮肤基底层中发现的主要结构形式。有六种与IV型胶原蛋白相关的人类基因，特别是COL 4A 1、COL 4A 2、COL 4A 3、COL 4A 4、COL 4A 5和COL 4A 6。这篇综述的目的是强调这种蛋白质在正常皮肤和某些疾病中的重要性。IV型胶原蛋白的α 3蛋白成分被认为是与肺出血肾炎综合征有关的抗原，其中免疫系统攻击肾小球和肺泡的基底膜。此外，编码IV型胶原蛋白的基因突变导致Alport综合征。此外，针对变性人IV型胶原的自身抗体已在类风湿性关节炎、硬皮病和SLE中描述。IV型胶原蛋白的结构研究已被用于区分表皮下水疱性疾病，包括大疱性类天疱疮、获得性大疱性表皮炎、抗癫痫蛋白瘢痕性类天疱疮和大疱性红斑狼疮。胶原蛋白IV在伤口愈合和胚胎发生中也是重要的。病理学研究表明，IV型胶原蛋白的微小结构差异可导致不同的临床不同疾病。
Type IV collagen is a type of collagen found primarily in the skin within the basement membrane zone. The type IV collagen C4 domain at the C-terminus is not removed in post-translational processing, and the fibers are thus link head-to-head, rather than in a parallel fashion. Also, type IV collagen lacks a glycine in every third amino-acid residue necessary for the tight collagen helix. Thus, the overall collagen-IV conformation is structurally more pliable and kinked, relative to other collagen subtypes. These structural features allow collagen IV to form sheets, which is the primary structural form found in the cutaneous basal lamina. There are six human genes associated with collagen IV, specifically COL4A1, COL4A2, COL4A3, COL4A4, COL4A5 and COL4A6. The aim of this review is to highlight the significance of this protein in normal skin, and in selected diseases. The alpha 3 protein constituent of type IV collagen is thought to be the antigen implicated in Goodpasture's syndrome, wherein the immune system attacks the basement membranes of the renal glomeruli and pulmonary alveoli. In addition, mutations to the genes coding for type IV collagen lead to the Alport syndrome. Furthermore, autoantibodies directed against denatured human type IV collagen have been described in rheumatoid arthritis, scleroderma, and SLE. Structural studies of collagen IV have been utilized to differentiate between subepidermal blistering diseases, including bullous pemphigoid, acquired epidermolysis bullosa, anti-epiligrin cicatricial pemphigoid, and bullous lupus erythematosus. Collagen IV is also of importance in wound healing and in embryogenesis. Pathological studies have demonstrated that minor structural differences in collagen IV can lead to distinct, clinically different diseases.