Overexpression of Bcl-2 protects from ultraviolet B-induced apoptosis but promotes hair follicle regression and chemotherapy-induced alopecia
Overexpression of Bcl-2 protects from ultraviolet B-induced apoptosis but promotes hair follicle regression and chemotherapy-induced alopecia
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DOI：
10.1016/s0002-9440(10)65008-0
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发表时间：
2000-04-01
影响因子：
6
通讯作者：
Kupper, TS
中科院分区：
文献类型：
--
作者：
Müller-Röver, S;Rossiter, H;Kupper, TS
毛囊 (HF) 生长和退化是细胞增殖的精细调节过程，随后是大量细胞死亡，并伴随着凋亡调节基因对 Bcl-2 和 Bar 的周期性表达。为了进一步研究 Bcl-2 表达在控制毛发生长和角质形成细胞凋亡中的作用，我们使用了在人 keratin-14 启动子控制下在基底表皮和外根鞘中过表达人 Bcl-2 的转基因小鼠(K14/Bcl-2)，当用紫外线 B (UVB) 光照射时，与野生型小鼠相比，K14/Bcl-2 小鼠表皮基底层中的晒伤细胞（凋亡的角质形成细胞）减少了约 5-10 倍，而来自转基因小鼠的原代角质形成细胞培养物在容易诱导野生型细胞释放组蛋白的剂量下，仅完全抵抗 UVB 诱导的组蛋白形成。 K14/Bcl-2 小鼠未表现出新生毛囊形态发生的改变或第一波 HF 消退（退行期）的开始。然而，与野生型对照相比，K14/Bcl-2 小鼠随后表现出自发退行期进展的显着加速。在化疗引起的脱发过程中，K14/Bcl-2 小鼠的毛囊营养不良得到促进。因此，尽管 K14 驱动的 Bcl-2 过度表达保护小鼠表皮角质形成细胞免受 UVB 诱导的细胞凋亡，但它令人惊讶地促进退行期和化疗相关的角质形成细胞凋亡。
Hair follicle (HF) growth and regression is an exquisitely regulated process of cell proliferation followed by massive cell death and is accompanied by cyclical expression of the apoptosis regulatory gene pair, Bcl-2 and Bar To further investigate the role of Bcl-2 expression in the control of hair growth and keratinocyte apoptosis, we have used transgenic mice that overexpress human Bcl-2 in basal epidermis and in the outer root sheath under the control of the human keratin-14 promoter (K14/Bcl-2), When irradiated with ultraviolet B (UVB) light, K14/Bcl-2 mice developed about 5-10-fold fewer sunburn cells tie, apoptotic keratinocytes) in the basal layer of the epidermis, compared to wild-type mice, whereas cultures of primary keratinocytes from transgenic mice mere completely resistant to UVB-induced histone formation, at doses that readily induced histone release from wild-type cells. K14/ Bcl-2 mice show no alteration of neonatal hair follicle morphogenesis or of the onset of the first wave of HF regression (catagen). However, compared to wild-type controls, K14/Bcl-2 mice subsequently displayed a significant acceleration of spontaneous catagen progression. During chemotherapy-induced alopecia, follicular dystrophy was promoted in K14/Bcl-2 mice. Thus, although K14- driven overexpression of Bcl-2 protected murine epidermal keratinocytes from UVB-induced apoptosis, it surprisingly promoted catagen- and chemotherapy-associated keratinocyte apoptosis.