Crawford Melissa, Dagnino Lina
a Department of Physiology and Pharmacology , Children's Health Research Institute and Lawson Health Research Institute, The University of Western Ontario , London , Ontario , Canada.
Tissue Barriers. 2017 Oct 2;5(4):e1341969. doi: 10.1080/21688370.2017.1341969. Epub 2017 Jun 30.
The skin of mammals and other terrestrial vertebrates protects the organism against the external environment, preventing heat, water and electrolyte loss, as well as entry of chemicals and pathogens. Impairments in the epidermal permeability barrier function are associated with the genesis and/or progression of a variety of pathological conditions, including genetic inflammatory diseases, microbial and viral infections, and photodamage induced by UV radiation. In mammals, the outside-in epidermal permeability barrier is provided by the joint action of the outermost cornified layer, together with assembled tight junctions in granular keratinocytes found in the layers underneath. Tight junctions serve as both outside-in and inside-out barriers, and impede paracellular movements of ions, water, macromolecules and microorganisms. At the molecular level, tight junctions consist of integral membrane proteins that form an extracellular seal between adjacent cells, and associate with cytoplasmic scaffold proteins that serve as links with the actin cytoskeleton. In this review, we address the roles that scaffold proteins play specifically in the establishment and maintenance of the epidermal permeability barrier, and how various pathologies alter or impair their functions.
哺乳动物和其他陆生脊椎动物的皮肤保护机体免受外部环境影响，防止热量、水分和电解质流失，以及化学物质和病原体的侵入。表皮通透性屏障功能受损与多种病理状况的发生和/或进展相关，包括遗传性炎症性疾病、微生物和病毒感染以及紫外线辐射引起的光损伤。在哺乳动物中，由最外层角质化层以及其下方各层颗粒角质形成细胞中组装的紧密连接共同作用，形成由外向内的表皮通透性屏障。紧密连接既是由外向内的屏障，也是由内向外的屏障，可阻碍离子、水、大分子和微生物的细胞旁移动。在分子水平上，紧密连接由整合膜蛋白组成，这些蛋白在相邻细胞之间形成细胞外密封，并与作为肌动蛋白细胞骨架连接的细胞质支架蛋白相关联。在本综述中，我们阐述了支架蛋白在表皮通透性屏障的建立和维持中所起的具体作用，以及各种病理状况如何改变或损害其功能。
