Ting Stephen B, Caddy Jacinta, Hislop Nikki, Wilanowski Tomasz, Auden Alana, Zhao Lin-Lin, Ellis Sarah, Kaur Pritinder, Uchida Yoshikazu, Holleran Walter M, Elias Peter M, Cunningham John M, Jane Stephen M
Rotary Bone Marrow Research Laboratories, c/o Royal Melbourne Hospital Post Office, Grattan Street, Parkville, Victoria, Australia 3050.
Science. 2005 Apr 15;308(5720):411-3. doi: 10.1126/science.1107511.
The Drosophila cuticle is essential for maintaining the surface barrier defenses of the fly. Integral to cuticle resilience is the transcription factor grainy head, which regulates production of the enzyme required for covalent cross-linking of the cuticular structural components. We report that formation and maintenance of the epidermal barrier in mice are dependent on a mammalian homolog of grainy head, Grainy head-like 3. Mice lacking this factor display defective skin barrier function and deficient wound repair, accompanied by reduced expression of transglutaminase 1, the key enzyme involved in cross-linking the structural components of the superficial epidermis. These findings suggest that the functional mechanisms involving protein cross-linking that maintain the epidermal barrier and induce tissue repair are conserved across 700 million years of evolution.
果蝇的表皮对于维持果蝇的表面屏障防御至关重要。表皮韧性不可或缺的是转录因子颗粒头，它调节表皮结构成分共价交联所需酶的产生。我们报告称，小鼠表皮屏障的形成和维持依赖于颗粒头的哺乳动物同源物颗粒头样3。缺乏该因子的小鼠表现出有缺陷的皮肤屏障功能和受损的伤口修复能力，同时转谷氨酰胺酶1（参与浅表表皮结构成分交联的关键酶）的表达降低。这些发现表明，涉及蛋白质交联以维持表皮屏障和诱导组织修复的功能机制在7亿年的进化过程中是保守的。
