Control of murine hair follicle regression (catagen) by TGF-β1 in vivo
Control of murine hair follicle regression (catagen) by TGF-β1 in vivo
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DOI：
10.1096/fasebj.14.5.752
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发表时间：
2000-04-01
期刊：
影响因子：
4.8
通讯作者：
Paus, R
中科院分区：
文献类型：
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作者：
Foitzik, K;Lindner, G;Paus, R
毛发周期的退化阶段（退化期）是一个伴随着终末分化、蛋白水解和基质重塑的脱发驱动过程。作为角质形成细胞增殖的抑制剂和角质形成细胞凋亡的诱导剂，转化生长因子β 1（TGF-β 1）已被认为在退行期调节中发挥重要作用。例如，在毛发周期的生长期后期和退化期开始时，TGF-β 1及其受体的最大表达表明了这一点。我们研究了TGF-β 1在退行期控制中的潜在参与。我们比较了TGF-β 1基因敲除小鼠和年龄匹配的野生型同窝小鼠毛囊第一次自发进入退化期的情况，并评估了TGF-β 1注射对小鼠体内生长期毛囊的影响。在感染后第18天，TGF-β 1 -/-小鼠的毛囊仍处于退化期早期，而+/+同窝出生的小鼠的毛囊已经进入随后的静止期（休止期）。TGF-β 1 -/-小鼠显示更多的Ki-67阳性细胞和更少的凋亡细胞比相当的退化期卵泡+/+小鼠。相反，将TGF-β 1注射到小鼠背部皮肤中诱导了过早的退行期发育。此外，与对照组相比，TGF-β 1处理的小鼠中增殖的毛囊角质形成细胞的数量减少，TUNEL +细胞的数量增加。TGF-β II型受体（TGFRII）和TUNEL反应性的双重可视化显示了退行期卵泡中凋亡细胞核和TGFRII的共定位。这些数据强烈支持TGF-β 1可能通过抑制角质形成细胞增殖和诱导细胞凋亡，在体内退行期诱导的难以捉摸的内源性调节剂中排名。因此，TCF-β RII激动剂和拮抗剂可以为基于过早或延迟的退行期发育的人类毛发生长障碍（脱发、脱发、多毛症）提供有用的治疗工具。
The regression phase of the hair cycle (catagen) is an apoptosis-driven process accompanied by terminal differentiation, proteolysis, and matrix remodeling. As an inhibitor of keratinocyte proliferation and inductor of keratinocyte apoptosis, transforming growth factor beta 1 (TGF-beta 1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF-beta 1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF-beta 1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF-beta 1 null mice and age-matched wild-type littermates, and assessed the effects of TGF-beta 1 injection on murine anagen hair follicles in vivo. At day 18 p.p., hair follicles in TGF-beta 1 -/- mice were still in early catagen, whereas hair follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF-beta 1 -/- mice displayed more Ki-67-positive cells and fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF-beta 1 into the back skin of mice induced premature catagen development. In addition, the number of proliferating follicle keratinocytes was reduced and the number of TUNEL + cells was increased in the TGF-beta 1-treated mice compared to controls. Double visualization of TGF-beta type II receptor (TGFRII) and TUNEL reactivity revealed colocalization of apoptotic nuclei and TGFRII in catagen follicles. These data strongly support that TGF-beta 1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte proliferation and induction of apoptosis. Thus, TCF-beta RII agonists and antagonists may provide useful therapeutic tools for human hair growth disorders based on premature or retarded catagen development (effluvium, alopecia, hirsutism).