Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis

Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis
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DOI:
10.1093/emboj/18.17.4657
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发表时间:
1999-09-01
期刊:
影响因子:
11.4
通讯作者:
Takeda, J
Takeda, J
中科院分区:
生物学1区
文献类型:
--
作者:
Sano, S;Itami, S;Takeda, J

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为了阐明Stat 3在皮肤中的生物学作用,使用Cre-loxP系统进行条件性基因靶向,因为种系Stat 3消融导致胚胎致死。K5-Cre; Stat 3(flox/-)转基因小鼠的表皮和毛囊角质形成细胞缺乏功能性Stat 3,其表皮和毛囊发育正常,但毛发周期和伤口愈合过程严重受损。此外,突变小鼠表达稀疏的毛发,并随着年龄的增长自发发生溃疡。尽管正常的增殖反应,生长因子依赖的Stat 3破坏角质形成细胞的体外迁移受损。因此,我们的结论是,Stat 3起着至关重要的作用,在转导所需的迁移,但不是角质形成细胞增殖的信号,和Stat 3是必不可少的皮肤重塑,包括头发周期和伤口愈合。
To elucidate the biological role of Stat3 in the skin, conditional gene targeting using the Cre-loxP system was performed as germline Stat3 ablation leads to embryonic lethality. K5-Cre;Stat3(flox/-) transgenic mice, whose epidermal and follicular keratinocytes lack functional Stat3, were viable and the development of epidermis and hair follicles appeared normal, However hair cycle and wound healing processes mere severely compromised. Furthermore, mutant mice expressed sparse hair and developed spontaneously occurring ulcers with age. Growth factor-dependent in vitro migration of Stat3-disrupted keratinocytes was impaired despite normal proliferative responses. We therefore conclude that Stat3 plays a crucial role in transducing a signal required for migration but not for proliferation of keratinocytes, and that Stat3 is essential for skin remodeling, including hair cycle and wound healing.