Hair cycle and wound healing in mice with a keratinocyte-restricted deletion of FAK
Hair cycle and wound healing in mice with a keratinocyte-restricted deletion of FAK
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DOI：
10.1038/sj.onc.1209130
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发表时间：
2006-02-01
期刊：
影响因子：
8
通讯作者：
Ilic, D
中科院分区：
文献类型：
--
作者：
Essayem, S;Kovacic-Milivojevic, B;Ilic, D
局灶黏附激酶（FAK）是整合素和生长因子受体下游转导信号的关键成分。为了确定FAK的缺失如何影响体内表皮，我们建立了角质形成细胞限制FAK缺失的小鼠模型（FAK（K5 KO）小鼠）。FAKK5 KO小鼠表现出三种主要表型——毛发周期不规则、皮脂腺发育不全和表皮变薄——这表明在凸起处发现的多能干细胞的增殖能力存在缺陷。在常规原代培养中，fak缺失的角质形成细胞会发生大量凋亡，阻碍了进一步的分析，而在体内观察到的缺陷并不会缩短小鼠的寿命。这些结果表明，原生组织的结构和信号环境可能通过FAK克服信号的缺乏。我们的发现指出了体内和体外三维模型在细胞迁移、增殖和存活分析中的重要性。令人惊讶的是，FAK（loxP/+）和FAK(K5) （KO）小鼠在伤口愈合方面的差异没有统计学意义，这表明体内FAK的缺失不会像影响皮肤多能干细胞那样影响基底角化细胞的迁移/增殖。
Focal adhesion kinase (FAK) is a critical component in transducing signals downstream of both integrins and growth factor receptors. To determine how the loss of FAK affects the epidermis in vivo, we have generated a mouse model with a keratinocyte-restricted deletion of fak (FAK(K5 KO) mice). FAKK5 KO mice displayed three major phenotypes-irregularities of hair cycle, sebaceous glands hypoplasia, and a thinner epidermis-pointing to defects in the proliferative capacity of multipotent stem cells found in the bulge. FAK-null keratinocytes in conventional primary culture undergo massive apoptosis hindering further analyses, whereas the defects observed in vivo do not shorten the mouse lifespan. These results suggest that the structure and the signaling environment of the native tissue may overcome the lack of signaling through FAK. Our findings point to the importance of in vivo and three-dimensional in vitro models in analyses of cell migration, proliferation, and survival. Surprisingly, the difference between FAK(loxP/+) and FAK(K5) (KO) mice in wound closure was not statistically significant, suggesting that in vivo loss of FAK does not affect migration/proliferation of basal keratinocytes in the same way as it affects multipotent stem cells of the skin.