In Vivo Evidence for a Bridging Role of a Collagen V Subtype at the Epidermis-Dermis Interface
In Vivo Evidence for a Bridging Role of a Collagen V Subtype at the Epidermis-Dermis Interface
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DOI：
10.1038/jid.2012.56
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发表时间：
2012-07-01
影响因子：
6.5
通讯作者：
Ruggiero, Florence
中科院分区：
文献类型：
--
作者：
Bonod-Bidaud, Christelle;Roulet, Muriel;Ruggiero, Florence
V型胶原蛋白是大多数典型ehers - danlos综合征（EDS）病例中的缺陷产物，EDS是一种结缔组织疾病，典型特征是皮肤脆弱和伤口愈合异常。胶原蛋白V组装成不同的分子形式。主要的α 1(V)(2) α 2(V)异源三聚体控制皮肤和其他组织的纤维形成。α 1(V)(3)次要形式被认为存在于皮肤中，但其功能尚不清楚。为了阐明其作用，我们培育了在表皮中过表达人类α 1(V)(3)同源三聚体的转基因小鼠。转基因衍生产物以薄而无条纹的纤维状物质沉积在基底膜2（胚胎和围产期表皮和毛囊之一）中。含有α 1(V)(3)的原纤维的积累导致表皮-真皮界面的超微结构改变，并引起生物力学特性的变化，尽管没有统计学意义。使用超顺磁免疫珠分离真实的上层结构和蛋白质结合实验，我们证明了同型三聚体是包含胶原IV、层粘连蛋白111和真皮胶原VI的蛋白质网络的一部分。我们的数据表明，同型三聚体作为桥接分子，有助于表皮-真皮界面的稳定。这一发现强烈提示胶原V可能在皮肤中以不同亚型表达，在基质组织和稳定性中发挥重要但不同的作用。Journal of Investigative Dermatology (2012) 132, 1841-1849；doi: 10.1038 / jid.2012.56;2012年3月22日在线发布
Collagen V is the defective product in most cases of classical Ehlers-Danlos syndrome (EDS), a connective tissue disorder typically characterized by skin fragility and abnormal wound healing. Collagen V assembles into diverse molecular forms. The predominant alpha 1(V)(2)alpha 2(V) heterotrimer controls fibrillogenesis in skin and other tissues. The alpha 1(V)(3) minor form is thought to occur in skin, but its function is unknown. To elucidate its role, we generated transgenic mice that overexpress the human alpha 1(V)(3) homotrimer in the epidermis. The transgenederived product is deposited as thin unstriated fibrillar material in the basement membrane 2:one of embryonic and perinatal epidermis and hair follicles. Accumulation of alpha 1(V)(3)-containing fibrils leads to ultrastructural modifications at the epidermis-dernnis interface and provokes changes in biomechanical properties, although not statistically significant. Using superparamagnetic immunobeads to isolate authentic suprastructures and protein-binding assays, we demonstrate that the homotrimer is part of a protein network containing collagen IV, laminin-111, and the dermal collagen VI. Our data show that the homotrimer serves as a bridging molecule that contributes to the stabilization of the epidermal-dermal interface. This finding strongly suggests that collagen V may be expressed in skin as different subtypes with important but distinct roles in matrix organization and stability. Journal of Investigative Dermatology (2012) 132, 1841-1849; doi:10.1038/jid.2012.56; published online 22 March 2012