Functional role of β1 integrin-mediated signalling in the human hair follicle

Functional role of β1 integrin-mediated signalling in the human hair follicle
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DOI:
10.1016/j.yexcr.2007.10.030
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发表时间:
2008-02-01
影响因子:
3.7
通讯作者:
Paus, R.
Paus, R.
中科院分区:
医学3区
文献类型:
--
作者:
Kloepper, J. E.;Hendrix, S.;Paus, R.

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被引文献

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整合素是跨膜粘附蛋白,可传递关键的拓扑生物学信息并发挥关键的信号传导功能。在皮肤和毛囊生物学中,β1 整合素及其配体特别令人感兴趣。目前尚不清楚β1整合素是否在人类毛发生长的调节中发挥作用,并且β1整合素在人类毛囊皮脂腺单位中的表达模式仍然不明确。在这里,我们在原位和体外证明,毛囊皮脂腺对[l整合素的免疫反应活性在人头皮毛囊的外根鞘的最外层和周围的结缔组织鞘中最为突出。 pi 整合素免疫反应位点共表达纤连蛋白和腱蛋白-C。与之前的报道相反,β1整合素原位免疫活性在人体凸起区域并未显着上调。从功能上讲,两种 β1 整合素激活抗体(12G10、TS2/16)和模拟配体 RGD 肽可促进体外显微解剖、器官培养的人头皮毛囊的生长,并抑制自发毛囊退化。这支持了β1整合素介导的信号传导在人类毛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是一种潜在的研究工具,用于探索β1整合素介导的信号传导的靶向刺激是否适合人类脱发管理。 (c) 2007 Elsevier Inc. 保留所有权利。
Integrins are transmembrane adhesion proteins that convey critical topobiological information and exert crucial signalling functions. in skin and hair follicle biology, beta 1 integrins and their ligands are of particular interest. It is not yet known whether beta 1 integrins play any role in the regulation of human hair growth and the expression pattern of beta 1 integrin in the human pilosebaceous unit remains ill-defined. Here, we show that pilosebaceous immunore activity for [ l 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 pi integrin immunoreactivity co-express fibronectin and tenascin-C. Contrary to previous reports, beta 1 integrin immunore activity in situ was not significantly upregulated in the human bulge region. Functionally, two beta 1 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 beta 1 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 beta 1 integrin-mediated signalling is a suitable candidate for human hair loss management. (c) 2007 Elsevier Inc. All rights reserved.