Diamond A Godwin, Gonterman Ryan M, Anderson Aileen L, Menon Keshav, Offutt Carlos D, Weaver Chad H, Philbrick William M, Foley John
Department of Medical Sciences, Indiana University School of Medicine, Bloomington, 47405, USA.
J Invest Dermatol. 2006 Sep;126(9):2127-34. doi: 10.1038/sj.jid.5700338. Epub 2006 May 4.
In developing organs, parathyroid hormone (PTH)/parathyroid hormone-related protein (PTHrP) receptor (PPR) signaling inhibits proliferation and differentiation of mesenchyme-derived cell types resulting in control of morphogenic events. Previous studies using PPR agonists and antagonists as well as transgenic overexpression of the PPR ligand PTHrP have suggested that this ligand receptor combination might regulate the anagen to catagen transition of the hair cycle. To further understand the precise role of PTHrP and the PPR in the hair cycle, we have evaluated hair growth in the traditional K14-PTHrP (KrP) and an inducible bitransgenic PTHrP mice. High levels of PTHrP trangene expression limited to the adult hair cycle resulted in the production of shorter hair shafts. Morphometric analysis indicated that reduced proliferation in the matrix preceded the appearance of thinner hair follicles and shafts during late anagen. CD31 staining revealed that the late anagen hair follicles of the KrP mice were surrounded by reduced numbers of smaller diameter capillaries as compared to controls. Moreover, the fetal skins of the PTHrP and PPR knockouts (KOs) had reciprocal increases in the length, diameter, and density of capillaries. Finally, crossing the KrP transgene onto a thrombospondin-1 KO background reversed the vascular changes as well as the delayed catagen exhibited by these mice. Taken together, these findings suggest that PTHrP's influence on the hair cycle is mediated in part by its effects on angiogenesis.
在发育中的器官中，甲状旁腺激素（PTH）/甲状旁腺激素相关蛋白（PTHrP）受体（PPR）信号传导抑制间充质来源细胞类型的增殖和分化，从而控制形态发生事件。先前使用PPR激动剂和拮抗剂以及PPR配体PTHrP转基因过表达的研究表明，这种配体-受体组合可能调节毛发周期的生长期向退行期的转变。为了进一步了解PTHrP和PPR在毛发周期中的精确作用，我们评估了传统的K14-PTHrP（KrP）小鼠和可诱导的双转基因PTHrP小鼠的毛发生长情况。仅限于成年毛发周期的高水平PTHrP转基因表达导致毛干变短。形态计量分析表明，在生长期后期，毛囊基质中增殖减少先于毛囊和毛干变细。CD31染色显示，与对照组相比，KrP小鼠生长期后期的毛囊周围直径较小的毛细血管数量减少。此外，PTHrP和PPR基因敲除（KO）小鼠的胎儿皮肤中毛细血管的长度、直径和密度呈相反增加。最后，将KrP转基因与血小板反应蛋白-1基因敲除背景杂交，逆转了这些小鼠的血管变化以及延迟的退行期。综上所述，这些发现表明PTHrP对毛发周期的影响部分是由其对血管生成的作用介导的。
