Madison Kathi C
Marshall Dermatology Research Laboratories, Department of Dermatology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa, USA.
J Invest Dermatol. 2003 Aug;121(2):231-41. doi: 10.1046/j.1523-1747.2003.12359.x.
The primary function of the epidermis is to produce the protective, semi-permeable stratum corneum that permits terrestrial life. The barrier function of the stratum corneum is provided by patterned lipid lamellae localized to the extracellular spaces between corneocytes. Anucleate corneocytes contain keratin filaments bound to a peripheral cornified envelope composed of cross-linked proteins. The many layers of these specialized cells in the stratum corneum provide a tough and resilient framework for the intercellular lipid lamellae. The lamellae are derived from disk-like lipid membranes extruded from lamellar granules into the intercellular spaces of the upper granular layer. Lysosomal and other enzymes present in the extracellular compartment are responsible for the lipid remodeling required to generate the barrier lamellae as well as for the reactions that result in desquamation. Lamellar granules likely originate from the Golgi apparatus and are currently thought to be elements of the tubulo-vesicular trans-Golgi network. The regulation of barrier lipid synthesis has been studied in a variety of models, with induction of several enzymes demonstrated during fetal development and keratinocyte differentiation, but an understanding of this process at the molecular genetic level awaits further study. Certain genetic defects in lipid metabolism or in the protein components of the stratum corneum produce scaly or ichthyotic skin with abnormal barrier lipid structure and function. The inflammatory skin diseases psoriasis and atopic dermatitis also show decreased barrier function, but the underlying mechanisms remain under investigation. Topically applied "moisturizers" work by acting as humectants or by providing an artificial barrier to trans-epidermal water loss; current work has focused on developing a more physiologic mix of lipids for topical application to skin. Recent studies in genetically engineered mice have suggested an unexpected role for tight junctions in epidermal barrier function and further developments in this area are expected. Ultimately, more sophisticated understanding of epidermal barrier function will lead to more rational therapy of a host of skin conditions in which the barrier is impaired.
表皮的主要功能是产生具有保护作用的半透性角质层，从而使陆地生活成为可能。角质层的屏障功能由定位于角质形成细胞之间细胞外间隙的规则排列的脂质片层提供。无核角质形成细胞含有与由交联蛋白组成的外周角化包膜结合的角蛋白丝。角质层中这些特殊细胞的多层结构为细胞间脂质片层提供了坚韧且有弹性的框架。这些片层源自从板层颗粒挤出到上层颗粒层细胞间间隙的盘状脂质膜。细胞外区室中存在的溶酶体酶和其他酶负责生成屏障片层所需的脂质重塑以及导致脱屑的反应。板层颗粒可能起源于高尔基体，目前被认为是管状小泡反式高尔基体网络的组成部分。屏障脂质合成的调控已在多种模型中进行了研究，在胎儿发育和角质形成细胞分化过程中几种酶被诱导表达，但在分子遗传学水平上对这一过程的理解仍有待进一步研究。脂质代谢或角质层蛋白质成分的某些遗传缺陷会导致皮肤出现鳞屑或鱼鳞病样改变，伴有异常的屏障脂质结构和功能。炎症性皮肤病银屑病和特应性皮炎也表现出屏障功能下降，但其潜在机制仍在研究中。局部应用的“保湿剂”通过充当保湿剂或为经表皮水分流失提供人工屏障来发挥作用；目前的工作重点是开发更符合生理的脂质混合物用于局部皮肤应用。最近对基因工程小鼠的研究表明紧密连接在表皮屏障功能中具有意想不到的作用，预计该领域将有进一步的进展。最终，对表皮屏障功能更深入的理解将导致对许多屏障受损的皮肤疾病进行更合理的治疗。
