PTHrP regulates epidermal differentiation in adult mice
PTHrP regulates epidermal differentiation in adult mice
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DOI：
10.1046/j.1523-1747.1998.00428.x
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发表时间：
1998-12-01
影响因子：
6.5
通讯作者：
Philbrick, WM
中科院分区：
文献类型：
--
作者：
Foley, J;Longely, BJ;Philbrick, WM
新出现的证据表明，甲状旁腺素相关肽（PTHrP）作为一个调节器的发展和/或分化的一些器官，包括软骨内骨，牙齿，和乳腺。尽管通过同源重组破坏PTHrP基因导致致命的软骨营养不良，但是通过软骨中肽的转基因替代而被拯救的PTHrP敲除小鼠在包括皮肤在内的外胚层衍生结构中显示异常。在6-8周龄时，这些获救的PTHrP敲除小鼠表现出明显变薄的表皮和显著的角化过度、皮脂腺发育不全和纤维化真皮。与此相反，过度表达PTHrP的转基因小鼠凭借人角蛋白-14启动子显示增厚的腹侧表皮与显着的棘皮症和乳头状瘤，增生的皮脂腺，和细胞真皮。PTHrP的缺乏似乎导致基底角质形成细胞室的减少和过早获得基底上和颗粒分化标志物，而肽的过表达产生相互的结果。在PTHrP缺失的皮肤中没有发现表皮增殖率的差异，尽管在角蛋白14-PTHrP转基因动物中观察到增加，但它们的表皮不表达增生标记物Kb。最后，在角蛋白14启动子的指导下，在获救的PTHrP敲除小鼠的基底角质形成细胞中PTHrP的替换逆转了在PTHrP缺失的皮肤中观察到的异常。这些发现表明PTHrP调节成年小鼠皮肤中角质形成细胞分化的速率。
Emerging evidence suggests that parathyroid hormone-related peptide (PTHrP) serves as a regulator of the development and/or differentiation of a number of organs, including endochondral bone, the tooth, and the mammary gland. Although disruption of the PTHrP gene by homologous recombination results in a lethal chondrodystrophy, PTHrP-knockout mice that have been rescued by the transgenic replacement of the peptide in cartilage display abnormalities in ectodermally derived structures including the skin. At 6-8 wk of age, these rescued PTHrP-knockout mice displayed a markedly thinned epidermis and striking hyperkeratosis, hypoplastic sebaceous glands, and a fibrotic dermis. In contrast, transgenic mice that overexpress PTHrP by virtue of the human keratin-14 promoter displayed a thickened ventral epidermis with marked acanthosis and papillomatosis, hyperplastic sebaceous glands, and a cellular dermis. The absence of PTHrP appeared to result in the reduction of the basal keratinocyte compartment and premature acquisition of suprabasal and granular differentiation markers, whereas overexpression of the peptide generated reciprocal findings. No difference in the epidermal proliferation rate was found in PTHrP-null skin and although an increase was observed in keratin 14-PTHrP transgenic animals, their epidermis did not express the hyperplasia marker Kb, Finally, the replacement of PTHrP in the basal keratinocytes of rescued PTHrP-knockout mice under the direction of the keratin 14 promoter reversed the abnormalities seen in PTHrP-null skin. These findings suggest that PTHrP regulates the rate of keratinocyte differentiation in the skin of adult mice.