层黏连蛋332的生物学功能与相关皮肤病的研究进展

Biological Function of Laminin-332 and its Related Dermatosis

层黏连蛋白332(Laminin-332,Ln-332)是基底膜的主要成分之一,它是真表皮连接处锚定复合物中的关键分子,在维持基底膜完整性中发挥重要作用。该蛋白作为配体可与细胞跨膜蛋白整合素α6β4、α3β1等相互作用,参与细胞的黏附、迁移。在正常皮肤中,Ln-332通过与整合素α6β4及Ⅶ型胶原连接,将半桥粒附着于真皮。当基底膜遭到破坏时,Ln-332分泌快速增加,与整合素α3β1结合,作为细胞迁移的支架,促进角质形成细胞向创面迁移,从而加速伤口愈合。编码Ln-332的相关基因突变可导致交界性大疱性表皮松解症;而对Ln-332不同亚基的自身抗体可引起抗Ln-332型黏膜类天疱疮。此外,研究发现Ln-332可促进某些上皮来源肿瘤的侵袭、转移,参与形成肿瘤微环境。

Ln-332(Laminin-332,Ln-332)is an essential component of the dermal-epidermal junction,which attaches the epidermis to the dermis and plays a key role in maintaining the integrity of basement membrane zone.As a ligand,Ln-332 can interact with several transmembrane receptors(includingα6β4-andα3β1-integrins).Thereby regulating keratinocyte adhesion and motility.In intact skin,Ln-332 provides essential links to both the hemidesmosomalα6β4-integrin and the collagen typeⅦmolecules which form the anchoring fibrils inserting into the dermis.When skin injured,Ln-332 production increases rapidly,then it is regarded as a scaffold for cells migration,promotes the migration of keratinocytes to the wound surface and accelerates wound healing.Mutations of the Ln-332 genes or auto-antibodies against one of the subunits of ln-332 may lead to junctional epidermolysis bullosa and mucous membrane pemphigoid,respectively.In addition,Ln-332 has been found to promote the invasion and metastasis of some epithelial-derived tumors and participate in the formation of tumor microenvironment.