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β1整合素介导的信号传导在人毛囊中的功能作用。

Functional role of beta 1 integrin-mediated signalling in the human hair follicle.

作者信息

Kloepper J E, Hendrix S, Bodó E, Tiede S, Humphries M J, Philpott M P, Fässler R, Paus R

机构信息

Department of Dermatology, Allergology and Venerology, University Hospital of Schleswig-Holstein, University of Lübeck, Lübeck, Germany.

出版信息

Exp Cell Res. 2008 Feb 1;314(3):498-508. doi: 10.1016/j.yexcr.2007.10.030. Epub 2007 Nov 12.

Abstract

Integrins are transmembrane adhesion proteins that convey critical topobiological information and exert crucial signalling functions. In skin and hair follicle biology, beta1 integrins and their ligands are of particular interest. It is not yet known whether beta1 integrins play any role in the regulation of human hair growth and the expression pattern of beta1 integrin in the human pilosebaceous unit remains ill-defined. Here, we show that pilosebaceous immunoreactivity for beta1 integrin is most prominent in the outermost layer of the outer root sheath and the surrounding connective tissue sheath of human scalp hair follicles in situ and in vitro. Sites of beta1 integrin immunoreactivity co-express fibronectin and tenascin-C. Contrary to previous reports, beta1 integrin immunoreactivity in situ was not significantly upregulated in the human bulge region. Functionally, two beta1 integrin-activating antibodies (12G10, TS2/16) and ligand-mimicking RGD peptides promoted the growth of microdissected, organ-cultured human scalp hair follicles in vitro and inhibited spontaneous hair follicle regression. This supports the concept that beta1 integrin-mediated signalling is also important in human hair growth control. The physiologically relevant organ culture assay employed here is a potential research tool for exploring whether targeted stimulation of beta1 integrin-mediated signalling is a suitable candidate for human hair loss management.

摘要

整合素是跨膜黏附蛋白,可传递关键的拓扑生物学信息并发挥重要的信号传导功能。在皮肤和毛囊生物学中,β1整合素及其配体尤其受到关注。β1整合素是否在人类头发生长调节中发挥作用尚不清楚,并且β1整合素在人皮脂腺单位中的表达模式仍不明确。在此,我们表明,β1整合素在人头皮毛囊外根鞘的最外层以及周围结缔组织鞘中的毛囊皮脂腺免疫反应性在原位和体外最为显著。β1整合素免疫反应性的位点共表达纤连蛋白和腱生蛋白-C。与先前的报道相反,β1整合素在人隆突区的原位免疫反应性并未显著上调。在功能上,两种β1整合素激活抗体(12G10、TS2/16)和模拟配体的RGD肽在体外促进了显微解剖、器官培养的人头皮毛囊的生长,并抑制了毛囊的自发退化。这支持了β1整合素介导的信号传导在人类头发生长控制中也很重要的概念。这里采用的生理相关器官培养测定法是一种潜在的研究工具,可用于探索靶向刺激β1整合素介导的信号传导是否是人类脱发管理的合适候选方法。

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