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Morophological analysis of the c-Kit expressing cells that control gastrointestinal motility

控制胃肠运动的 c-Kit 表达细胞的形态学分析

基本信息

批准号：
10670020
负责人：
NAKAMURA Kei-ichiro
金额：
$ 2.37万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670020/
关键词：
gastrointestinal motility pacemaker c-Kit gap junctions mast cells Interstitial cells of Cajal W mutant mice モルモット Interstitial cells of Caial W mutant マウス

项目摘要

1. We identified connexin45-expressing cells that form a cellular network in the deep muscular plexus layer of dog and rat small intestine by immunohistochemistry. By comparing guinea pig c-Kit positive cellular network, functional properties of connexin45 expressing cells are considered as a conduction system in the intestinal wall.2. Connexin43 expressing cells were also identified in the submuscular plexus of dog and guinea pig colon. Gap junctions were observed under electron microscopy between same type of cells and with surrounding smooth muscle cells.3. We observed spindle-shaped c-Kit immunopositive cells within circular muscle layer of guinea pigs and identified those cells were mast cells under electron microscopy.4. By immunohistochemistry, cells positive for both c-Kit and CD34 and positive singly for CD34 were identified in mouse colon muscular layer.5. By comparing W/WィイD1VィエD1 mutant and wild type mice, c-Kit positive cells within circular muscle layer of colon were found to be eliminated specifically in the mutant animals.Taken together, we conclude that c-Kit positive cells in deep muscular plexus form cellular network connected via connexin45 and work as a conduction system and interstitial cells of signal transmission between enteric nervous system and smooth muscle cells, and that those that form network in submuscular plexus of colon are connected via connexin43 gap junctions to form conduction system and pacemaker together with c-Kit positive cells within circular layer.We are planning experiments that clarify distribution and organization of specific cells type that are connected specific type of connexin molecules by in situ hybridization and by producing knockout mice of the specific connexin molecules in order to understand the mechanisms that regulate whole tissue motility other than enteric nervous system.

1.用免疫组织化学方法鉴定了犬和大鼠小肠深肌间神经丛中表达连接蛋白45的细胞，形成了细胞网络。通过比较豚鼠c-Kit阳性细胞网络，认为连接蛋白45表达细胞的功能特性是肠壁的一种传导系统。在犬和豚鼠结肠的肌下神经丛中也发现了连接蛋白43的表达细胞。在电子显微镜下观察到同类型细胞之间以及与周围的平滑肌细胞之间的缝隙连接。观察豚鼠环肌层内c-Kit免疫阳性细胞呈纺锤形，并在电子显微镜下鉴定为肥大细胞。免疫组织化学方法检测到小鼠结肠肌层c-Kit和CD34双阳性，CD34单阳性。通过对W/WィイD1VィエD1突变小鼠和野生型小鼠的比较，发现突变小鼠结肠环肌层c-Kit阳性细胞被特异性消除。综上所述，深肌丛中的c-Kit阳性细胞通过连接蛋白45形成细胞网络，在肠道神经系统和平滑肌细胞之间起着传导系统和间质细胞的作用。而在结肠肌下神经丛中形成网络的细胞通过连接蛋白43缝隙连接形成传导系统和起搏器，与环层内的c-Kit阳性细胞一起形成传导系统和起搏器。我们正在计划通过原位杂交和建立特定连接蛋白分子的敲除小鼠来阐明连接特定类型连接蛋白分子的特定细胞类型的分布和组织，以了解除肠道神经系统以外的整个组织运动的调节机制。