Oudhoff Menno J, Bolscher Jan G M, Nazmi Kamran, Kalay Hakan, van 't Hof Wim, Amerongen Arie V Nieuw, Veerman Enno C I
Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Department of Oral Biochemistry, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
FASEB J. 2008 Nov;22(11):3805-12. doi: 10.1096/fj.08-112003. Epub 2008 Jul 23.
Wounds in the oral cavity heal much faster than skin lesions. Among other factors, saliva is generally assumed to be of relevance to this feature. Rodent saliva contains large amounts of growth factors such as epidermal growth factor (EGF) and nerve growth factor (NGF). In humans, however, the identity of the involved compounds has remained elusive, especially since EGF and NGF concentrations are approximately 100,000 times lower than those in rodent saliva. Using an in vitro model for wound closure, we examined the properties of human saliva and the fractions that were obtained from saliva by high-performance liquid chromotography (HPLC) separation. We identified histatin 1 (Hst1) and histatin 2 (Hst2) as major wound-closing factors in human saliva. In contrast, the d-enantiomer of Hst2 did not induce wound closure, indicating stereospecific activation. Furthermore, histatins were actively internalized by epithelial cells and specifically used the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, thereby enhancing epithelial migration. This study demonstrates that members of the histatin family, which up to now were implicated in the antifungal weaponry of saliva, exert a novel function that likely is relevant for oral wound healing.
口腔伤口的愈合速度比皮肤损伤快得多。在诸多因素中，唾液通常被认为与这一特性有关。啮齿动物的唾液含有大量生长因子，如表皮生长因子（EGF）和神经生长因子（NGF）。然而，在人类中，相关化合物的身份一直难以确定，特别是因为EGF和NGF的浓度比啮齿动物唾液中的浓度低约10万倍。我们使用伤口闭合的体外模型，研究了人类唾液以及通过高效液相色谱（HPLC）分离从唾液中获得的组分的特性。我们确定组蛋白1（Hst1）和组蛋白2（Hst2）是人类唾液中主要的伤口闭合因子。相比之下，Hst2的d-对映体不会诱导伤口闭合，表明存在立体特异性激活。此外，组蛋白被上皮细胞主动内化，并特异性地利用细胞外信号调节激酶1/2（ERK1/2）途径，从而增强上皮细胞迁移。这项研究表明，组蛋白家族成员此前被认为与唾液的抗真菌作用有关，现在发挥了一种可能与口腔伤口愈合相关的新功能。
