Sano S, Itami S, Takeda K, Tarutani M, Yamaguchi Y, Miura H, Yoshikawa K, Akira S, Takeda J
Department of Dermatology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, USA.
EMBO J. 1999 Sep 1;18(17):4657-68. doi: 10.1093/emboj/18.17.4657.
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 were 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.
为阐明Stat3在皮肤中的生物学作用，由于生殖系Stat3缺失会导致胚胎致死，因此使用Cre-loxP系统进行了条件性基因靶向。K5-Cre;Stat3(flox/-)转基因小鼠的表皮和毛囊角质形成细胞缺乏功能性Stat3，它们能够存活，表皮和毛囊的发育看起来正常。然而，毛发周期和伤口愈合过程受到严重损害。此外，突变小鼠随着年龄增长毛发稀疏，并出现自发性溃疡。尽管Stat3缺失的角质形成细胞具有正常的增殖反应，但其依赖生长因子的体外迁移能力受损。因此，我们得出结论，Stat3在转导角质形成细胞迁移而非增殖所需的信号中起关键作用，并且Stat3对于包括毛发周期和伤口愈合在内的皮肤重塑至关重要。
