Hayashi Katsuhiko, Storesund Trond, Schreurs Olav, Khuu Cuong, Husvik Camilla, Karatsaidis Andreas, Helgeland Kristen, Martin-Zanca Dionisio, Schenck Karl
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Eur J Oral Sci. 2007 Oct;115(5):344-54. doi: 10.1111/j.1600-0722.2007.00480.x.
Nerve growth factor beta (NGF-beta) and its precursor proNGF are important for the differentiation and survival of neurons and dermal keratinocytes. The aim of this study was to determine the role that NGF might play in the differentiation and wound healing of oral mucosa. Cultured normal human oral mucosal keratinocytes expressed mRNA for NGF-beta/proNGF and for their receptors TrkA and p75(NTR). Lysates from cultured oral mucosal keratinocytes did not contain detectable amounts of mature 14-kDa NGF-beta but did contain several NGF proforms with molecular weights between 32 and 114 kDa. Culture medium from oral mucosal keratinocytes contained 75 kDa proNGF. The addition of NGF-beta significantly enhanced the proliferation of oral mucosal keratinocyte cultures and in vitro scratch closure. Immunostaining of biopsies from normal oral mucosa showed the presence of proNGF in all epithelial layers. NGF staining was observed in the granular and upper spinous cell layers. TrkA immunoreactivity was detected in basal and parabasal cells, with weak to moderate staining in spinous and granular cell layers. p75(NTR) staining was seen in basal cell layers. These findings indicate that NGF-beta/proNGF have mitogenic and motogenic effects on oral mucosal keratinocytes and therefore may aid in the healing of oral wounds. Differential expression of NGF and NGF receptors throughout the epithelium suggests a role in epithelial differentiation.
神经生长因子β（NGF-β）及其前体proNGF对神经元和真皮角质形成细胞的分化及存活至关重要。本研究的目的是确定NGF在口腔黏膜分化和伤口愈合中可能发挥的作用。培养的正常人口腔黏膜角质形成细胞表达NGF-β/proNGF及其受体TrkA和p75（NTR）的mRNA。培养的口腔黏膜角质形成细胞裂解物中未检测到可检测量的成熟14 kDa NGF-β，但确实含有几种分子量在32至114 kDa之间的NGF前体形式。口腔黏膜角质形成细胞的培养基中含有75 kDa proNGF。添加NGF-β显著增强了口腔黏膜角质形成细胞培养物的增殖和体外划痕闭合。正常口腔黏膜活检组织的免疫染色显示所有上皮层均存在proNGF。在颗粒层和棘层上层观察到NGF染色。在基底细胞和副基底细胞中检测到TrkA免疫反应性，在棘层和颗粒层中染色为弱阳性至中度。在基底细胞层中可见p75（NTR）染色。这些发现表明NGF-β/proNGF对口腔黏膜角质形成细胞具有促有丝分裂和促运动作用，因此可能有助于口腔伤口的愈合。NGF及其受体在整个上皮中的差异表达表明其在上皮分化中发挥作用。
