敲除非受体酪氨酸激酶c-Abl促进小鼠毛发循环和再生

Knockout of Non-receptor Tyrosine Kinase c-Abl Accelerates Hair Cycle and Regeneration in Mouse

c-Abl作为非受体酪氨酸激酶家族的成员,参与调节多个组织器官的发育过程,如神经、血管及骨骼等。c-Abl的异常激活也往往导致神经退行性疾病或肿瘤的发生。到目前为止,c-Abl在皮肤和毛发器官中的研究非常少。本研究首先分析了c-Abl基因在皮肤和毛囊中的动态表达情况,发现在毛囊上皮有丰富的表达,然后利用表皮特异性工具小鼠K14-Cre将c-Abl基因在表皮敲除,发现毛囊由静息期向生长期的转换略有加快。小鼠脱毛实验发现,当所有毛囊都从头开始再生时,突变鼠的毛囊起始比对照小鼠更快。这些结果均表明,在表皮敲除c-Abl基因能够导致毛发循环和毛囊再生的加快。进一步的研究发现,以上表型可能是c-Abl通过调节BMP信号通路造成的。我们的工作首次研究了c-Abl基因在皮肤毛囊中的动态表达,揭示了c-Abl通过BMP信号通路调节毛囊再生的机制。

c-Abl, a member of the non-receptor tyrosine kinase family, is involved in the regulation of multiple tissues and organs during development and morphorgenesis, such as nerves, blood vessels, and bones. Abnormal activation of c-Abl induces neurodegenerative diseases or tumorigenesis. However, very little research has been done on the skin and hair organs so far. In our research, we firstly analyzed the dynamic expression of c-Abl in the skin and hair follicle and found abundant c-Abl expression in the hair follicle epithelium. Hair follicle transition from telogen to anagen in K14-Cre ; c-Abl^f/f ; Arg^-/- mice was shown to be slightly faster than that in c-Abl^f/f; Arg^-/- control mice. Moreover, hair depilation experiment identified that hair follicles in mutant mouse grew faster than the control mice when all the hair follicles were beginning to regenerate. Both results indicated that c-Abl gene knoekout in the epidermis could accelerate hair cycle and regeneration. It was also found that c-Abl might function on hair development through BMP signaling pathway. Our works firstly showed the dynamic expression of c- Abl in skin epithelium and the mechanism by which c-Abl regulated hair follicle regeneration through the BMP signaling pathway.