IGF-I signalling controls the hair growth cycle and the differentiation of hair shafts
IGF-I signalling controls the hair growth cycle and the differentiation of hair shafts
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DOI：
10.1111/j.0022-202x.2005.23946.x
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发表时间：
2005-11-01
影响因子：
6.5
通讯作者：
Schlake, T
中科院分区：
文献类型：
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作者：
Weger, N;Schlake, T
真皮乳头和毛基质之间的间充质上皮信号传导调节成熟毛囊细胞的增殖和分化。这些相互作用的分子基础在很大程度上尚未被探索。根据其在真皮乳头中的表达，igf - 1可能参与了相互信号传导。为了进一步研究其在卵泡中的生物学功能，我们使用天合蛋白启动子片段产生了在根鞘和髓质中表达Igf-I的转基因小鼠。我们证明igf - 1影响毛囊增殖、组织重塑、头发生长周期以及毛囊分化。转基因皮肤在休止期暂时缺乏可见的脂肪组织。第二个异常生长阶段的开始明显迟缓。转基因护毛明显拉长，一小部分毛囊严重迷失方向。大多数毛轴的显微外观都发生了改变，令人惊讶的是，Igf-I转基因小鼠由于抑制毛轴弯曲而缺少锯齿状的毛发。Igfbp3的异位表达部分补偿了所有转基因效应。最后，Pdgfr α被确定为Igf-I转基因小鼠中第一个受影响的分子靶点。总之，我们的数据确定了igf - 1信号在毛囊生物学中是一个重要的有丝分裂和形态发生调节因子。
Mesenchymal-epithelial signalling between the dermal papilla and the hair matrix regulates cell proliferation and differentiation in mature hair follicles. The molecular basis of these interactions is largely unexplored. According to its expression in the dermal papilla, IGF-I is likely involved in reciprocal signalling. To examine its biological function in pelage follicles further, we generated transgenic mice that express Igf-I in the inner root sheath and the medulla using an involucrin promoter fragment. We demonstrate that Igf-I affects follicular proliferation, tissue remodelling, and the hair growth cycle, as well as folliclular differentiation. Transgenic skin temporarily lacks visible adipose tissue in telogen. The onset of the second, aberrant growth phase is markedly retarded. Transgenic guard hairs are significantly elongated and a small fraction of hair follicles is severely disoriented. The microscopic appearance of most hair shafts is altered and, strikingly, Igf-I transgenic mice lack hairs with a zigzag shape due to the suppression of hair shaft bending. All transgenic effects are partially compensated by ectopic expression of Igfbp3. Finally, Pdgfr alpha was identified as the first molecular target that is affected in Igf-I transgenic mice. In summary, our data identify IGF-I signalling as an important mitogenic and morphogenetic regulator in hair follicle biology.