Genetic pathways in disorders of epidermal differentiation.
Genetic pathways in disorders of epidermal differentiation.
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DOI：
10.1016/j.tig.2012.10.005
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Khavari PA
中科院分区：
文献类型：
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作者：
Lopez-Pajares V;Yan K;Zarnegar BJ;Jameson KL;Khavari PA
超过100种人类遗传性皮肤病，影响超过20%的人口，其特征在于破坏表皮分化。到目前为止，在这些疾病中鉴定的90个基因中有相当大的比例集中在几个功能通路中，这表明在表皮分化中出现了组织主题。其中包括Notch、TGFβ、IKK、Ras/MAPK、磷酸肌醇3-激酶、p63和Wnt信号通路以及介导钙稳态、组织完整性、角化和脂质生物合成的核心生物过程。在这里，我们回顾了最近的结果，支持这些途径在表皮分化中的核心作用，突出了遗传信息与功能研究的整合，以阐明这些途径在人类中的生物学作用，并指导未来治疗方法的开发，以纠正其功能障碍。
More than100 human genetic skin diseases, impacting over 20% of the population, are characterized by disrupted epidermal differentiation. A significant proportion of the 90 genes identified in these disorders to date are concentrated within several functional pathways, suggesting the emergence of organizing themes in epidermal differentiation. Among these are the Notch, TGFβ, IKK, Ras/MAPK, Phosphoinositide 3-kinase, p63, and Wnt signaling pathways as well as core biologic processes mediating calcium homeostasis, tissue integrity, cornification, and lipid biogenesis. Here, we review recent results supporting the central role of these pathways in epidermal differentiation, highlighting the integration of genetic information with functional studies to illuminate the biological actions of these pathways in humans as well as guide development of future therapeutics to correct their dysfunction.