三维重组人体皮肤模型在与表皮基底膜相关皮肤内稳态研究中的应用

Three-dimensional reconstructed human skin model: a powerful tool to study skin homeostasis and epidermal basement membrane morphogenesis

背景:日趋成熟的皮肤组织工程技术正在皮肤学的研究中发挥着越来越重要的作用。皮肤组织工程领域的重要研究内容之一就是构建具有完善的表皮基底膜的体外重组皮肤模型,这是因为表皮基底膜作为真皮和表皮的交界,将两大部分彼此连接起来,并且使表皮角质细胞和真皮成纤维细胞得以产生影响深远的交互作用。只有形成了正常的表皮基底膜,皮肤才具备了稳定性的基础。目的:综述表皮基底膜的结构和功能及其对皮肤内稳态的重要影响,同时总结三维重组人体皮肤模型在表皮基底膜研究中的应用,为相关的皮肤病理学和生理学研究提供解决方案。方法:以"skin"、"basement membrane"、"dermal epidermal junction"、"skin equivalent"、"reconstructed skin"、"skin homeostasis"为关键词,使用Pub Med数据库和Google学术搜索进行文献检索,检索时间范围为2000年1月至2016年9月的相关文献,并对检索结果进行筛选和排除,选择和本文研究目的高度相关的57篇文献进行综述。结果与结论:(1)近年来的研究显示表皮基底膜的作用不仅限于结构上的功能,它同时还具有选择性透过屏障的功能,并参与调节细胞行为、信号传导的过程,是表皮完整性和皮肤维持内稳态的基础,表皮基底膜分子的异常表达会导致皮肤出现病理学或生理学变化;(2)随着皮肤组织工程的发展,体外重建皮肤模型能够与人体皮肤在结构和组分上达到很好的相似性,从而成为表皮基底膜研究的重要手段,并且可应用于皮肤抗衰老研究和大疱性疾病的治疗中。

BACKGROUND:In recent years,skin tissue engineering technology has been well-developed and plays increasingly important roles in dermatology studies.The development of a functional epidermal basement membrane,also called dermal-epidermal junction,is one of the most sought after aspects of skin tissue engineering,and one of the hardest to recreate in vitro.At the dermal-epidermal junction level,dermal fibroblasts and epidermal keratinocytes interact to form an interlinked basement membrane of extracellular matrix,which forms as a concerted action of both keratinocytes and fibroblasts.Successful formation of this basement membrane is essential for the stability of human skin.OBJECTIVE:To summarize the molecular organization and impact of epidermal basement membrane on skin homeostasis,and to review the applications of reconstructed human skin model in epidermal basement membrane studies,providing solutions for related dermato-pathological and physiological issues.METHODS:A computer-based online search was performed in PubMed database and Google Scholar with the defined publication date ranging from 2000 until September 2016.The keywords were“skin,basement membrane,dermal epidermal junction,skin equivalent,reconstructed skin,skin homeostasis”.Finally 57 pertinent articles were screened out of the preliminary retrival list for further analysis.RESULTS AND CONCLUSION:Epidermal basement membrane is shown to play gate-keeping roles,which controls cellular behavior and diffusion of bioactive molecules via outside-in signaling.It is the foundation of epidermal integrity and skin homeostasis.The abnormal expression of basement membrane molecules will lead to skin physiological changes and even skin diseases.In vitro reconstructed skin model,highly resembling the normal human skin in structure and molecular organization,is becoming a very powerful tool to study the physiology of epidermal basement membrane,and also very promising for skin anti-aging research and the treatment of blistering diseases caused by epidermal basement membrane disorders.