Bull J J, Pelengaris S, Hendrix S, Chronnell C M T, Khan M, Philpott M P
Centre for Cutaneous Research, Barts and The London School of Medicine and Dentistry, Queen Mary College, London E1 2AT, UK.
Br J Dermatol. 2005 Jun;152(6):1125-33. doi: 10.1111/j.1365-2133.2005.06458.x.
The hair follicle continually undergoes dynamic remodelling in a cyclical manner involving tightly coordinated patterns of cell proliferation, differentiation and apoptosis. The oncoprotein c-Myc is a key regulator of these events in epidermal keratinocytes, but its importance in the hair growth cycle has not previously been determined.
To determine the role of c-Myc in the hair growth cycle.
We characterized the hair follicle phenotype of transgenic mice that permit expression of a switchable form of c-Myc (c-Myc-ER) in the suprabasal epithelial layers of the epidermis and hair follicle.
c-Myc activation increased epithelial cell proliferation in the outer root sheath and distal hair follicle, without any substantial alteration in levels of apoptosis. Moreover, chronic c-Myc activation resulted in marked desynchronization of the murine hair growth cycle, uncoupling of hair cycle-related skin thickness and enlargement of the sebaceous gland.
These data implicate c-Myc in the control of hair growth cycling and hair cycle-related epidermal and sebaceous gland homeostasis. We suggest that c-Myc may be activating follicular stem cells either directly or indirectly and that this has important implications for control of the 'hair cycle clock', hair growth and epidermal maintenance.
毛囊以周期性方式持续经历动态重塑,涉及细胞增殖、分化和凋亡的紧密协调模式。原癌蛋白c-Myc是表皮角质形成细胞中这些事件的关键调节因子,但其在毛发生长周期中的重要性此前尚未确定。
确定c-Myc在毛发生长周期中的作用。
我们对转基因小鼠的毛囊表型进行了表征,这些小鼠允许在表皮和毛囊的基底上层表达可切换形式的c-Myc(c-Myc-ER)。
c-Myc激活增加了外根鞘和毛囊远端的上皮细胞增殖,而凋亡水平没有任何实质性改变。此外,慢性c-Myc激活导致小鼠毛发生长周期明显不同步,毛发周期相关的皮肤厚度解耦联以及皮脂腺增大。
这些数据表明c-Myc参与毛发生长周期以及与毛发周期相关的表皮和皮脂腺稳态的控制。我们认为c-Myc可能直接或间接激活毛囊干细胞,这对“毛发周期时钟”的控制、毛发生长和表皮维持具有重要意义。