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Neurotrophic factors and gastrointestinal mucosa

神经营养因子与胃肠粘膜

基本信息

批准号：
15590683
负责人：
ICHIKAWA Takafumi
金额：
$ 2.11万
依托单位：
KITASATO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590683/
关键词：
neurotrophic factor gastrointestinal mucosa mucin aging 実験潰瘍免疫組織化学表層粘液細胞 calcitonin gene-related peptide TrkA TrkB TrkC NGF BDNF NT-3

项目摘要

To further clarify the regulatory mechanisms of barrier homeostasis in the gastrointestinal mucosa, we determined whether the neurotrophic factors could have a role in regulating mucus metabolism.1. Neurotrophic factors and their receptors in the gastrointestinal mucosa.In this study, the mRNA expression of NGF, BDNF, and NT-3 was seen in the stomachs, small intestines, and colons in rats and mice. In contrast, the receptors for the neurotrophic factors were not immunohistochemically detected in the rat gastrointestinal mucosa.2. Nerve fibers in the gastrointestinal mucosa.The density of the CGRP nerve fibers was reduced in both the lamina propria and submucosa of the middle-aged rats compared to the young rats. CGRP stimulated the mucin biosynthesis in the cultured corpus mucosa from 7-week-old rats, but not from the 52-week-old rats.3. Investigation of recovery processes in the mucosal injury.We prepared aspirin-or acetic acid-induced mucosal lesions in the rat gastric mucosae and microscopically observed the alterations of the epithelial cells of the corpus mucosae stained with the anti-mucin monoclonal antibodies^RGM21, PGM34, and RGM26, developed in our laboratory. The appearance of specific mucin species was observed in the regenerating epithelia of the rat during the healing processes from acute and chronic gastric mucosal damage.4. Effect of the neurotrophic factors on mucin metabolism.The mucin biosynthesis in the cultured rat gastric mucosa was stimulated by EGF and HGF, but not by the major neurotrophic factors such as NGF, BDNF, and NT-3.In summary, these findings suggest that certain nerve fiber has an important role in regulating mucus metabolism, but the major neurotrophic factors such as NGF, BDNF, and NT-3, have no effect on mucin biosynthesis in rat gastric mucus cells directly.

为了进一步阐明胃肠粘膜屏障稳态的调节机制，我们确定了神经营养因子是否在调节黏液代谢中起作用。胃肠道粘膜的神经营养因子及其受体。本研究在大鼠和小鼠的胃、小肠和结肠中均观察到NGF、BDNF和NT-3 mRNA的表达。相比之下，大鼠胃肠道粘膜未检测到神经营养因子受体。胃肠道粘膜中的神经纤维。中年大鼠固有层和粘膜下层的CGRP神经纤维密度均低于年轻大鼠。CGRP能刺激7周龄大鼠培养的体黏膜中粘蛋白的生物合成，但对52周龄大鼠无刺激作用。粘膜损伤恢复过程的研究。我们制备阿司匹林或乙酸诱导的大鼠胃粘膜病变，并用实验室研制的抗黏液蛋白单克隆抗体^RGM21、PGM34和RGM26染色，显微镜下观察其粘膜上皮细胞的变化。在急性和慢性胃粘膜损伤愈合过程中，在大鼠再生上皮中观察到特异性粘蛋白种类的出现。神经营养因子对粘蛋白代谢的影响。EGF和HGF能促进培养大鼠胃粘膜黏液蛋白的生物合成，而NGF、BDNF、NT-3等主要神经营养因子不能促进培养大鼠胃粘膜黏液蛋白的生物合成。综上所述，某些神经纤维在调节黏液代谢中具有重要作用，但主要的神经营养因子如NGF、BDNF、NT-3等并没有直接影响大鼠胃黏液细胞黏液蛋白的生物合成。