表皮分化复合体的表观遗传调控及潜在药物靶点研究进展

S. Abhishek, Suresh Palamadai Krishnan
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引用次数: 48

摘要

哺乳动物皮肤的主要特征包括毛囊、毛囊间表皮和皮脂腺,所有这些都形成毛囊皮脂腺单位。表皮保护层经历一个有序/程序化的增殖和分化过程,最终形成由去核角质细胞组成的角质包膜。这些终末分化的细胞以循环的方式脱落,这一过程通过诱导或抑制表皮分化复合体(EDC)基因来调节。这些基因横跨人类染色体1q21的2mb区域,通过多种机制在表皮发育中发挥重要作用。这些机制中的每一种都使用一种独特的染色质重塑因子或表观遗传修饰因子。这些因素单独或联合调节表皮分化。牛皮癣和癌症等疾病在增殖和分化方面表现出异常,部分原因是这些表观遗传机制的失调。了解生理和上述病理背景下的现有机制不仅可以促进药物开发,还可以对现有的药物传递系统进行改进。
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Epidermal Differentiation Complex: A Review on Its Epigenetic Regulation and Potential Drug Targets
The primary feature of the mammalian skin includes the hair follicle, inter-follicular epidermis and the sebaceous glands, all of which form pilo-sebaceous units. The epidermal protective layer undergoes an ordered/programmed process of proliferation and differentiation, ultimately culminating in the formation of a cornified envelope consisting of enucleated corneocytes. These terminally differentiated cells slough off in a cyclic manner and this process is regulated via induction or repression of epidermal differentiation complex (EDC) genes. These genes, spanning 2 Mb region of human chromosome 1q21, play a crucial role in epidermal development, through various mechanisms. Each of these mechanisms employs a unique chromatin re-modelling factor or an epigenetic modifier. These factors act to regulate epidermal differentiation singly and/or in combination. Diseases like psoriasis and cancer exhibit aberrations in proliferation and differentiation through, in part, dysregulation in these epigenetic mechanisms. Knowledge of the existing mechanisms in the physiological and the aforesaid pathological contexts may not only facilitate drug development, it also can make refinements to the existing drug delivery systems.
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