Molecular mechanism of development of mammalian smooth mscle

哺乳动物平滑肌发育的分子机制

基本信息

批准号：
10470025
负责人：
NISHI Katsuhide
金额：
$ 8.45万
依托单位：
KUMAMOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

c-kit, a receptor-type tyrosine kinase may regulate development of smooth muscle tissue in the mammalian gastrointestinal tract. To illustrate how c-kit plays roles in the functional development of the smooth muscle tissue, we surveyed change in the population and function of c-kit-positive (c-kit^+) cells, i.e. interstitial cells of Cajal, in the developing gastrointestinal tract of BALB/c mice intraperitoneally injected with the neutralizing anti-c-kit-monoclonal antibody (ACK2) for 8 days after birth. In control animals, the c-kit^+ cells constructed networks, contacting with both enteric nervous system and smooth muscle layers, but not in the ACK2-treated animals that had impaired spontaneous contractility of the intestine because of lack of the c-kit^+ cells. that possessed rhythmic Ca^<2+>-activated Cl^-conductance. It is also found that the c-kit^+ cells in the pacemaker region of the small intestine arid the longitudinal smooth muscle cells developed from the same kit-positive precursor cells, depending upon the extent of kit signals.In smooth muscle cells dissociated from gastrointestinal tract of the ACK2-treated animals, dysfunction in the ryanodine-sensitive Ca^<2+> storage in the cytoplasm was suggested when tested with caffeine-induced Ca^<2+>-activated K^+ currents under voltage-clamp conditions and fura-2 fluorometric measurements of intracellular Ca^<2+> concentration. Altogether, it is suggested that c-kit plays important roles in regulating development of the function of mammalian gastrointestinal tract.

C-KIT，一种受体型酪氨酸激酶可能调节哺乳动物胃肠道的平滑肌组织的发展。 To illustrate how c-kit plays roles in the functional development of the smooth muscle tissue, we surveyed change in the population and function of c-kit-positive (c-kit^+) cells, i.e. interstitial cells of Cajal, in the developing gastrointestinal tract of BALB/c mice intraperitoneally injected with the neutralizing anti-c-kit-monoclonal antibody (ACK2) for 8出生后几天。在对照动物中，C-kit^+细胞构建了网络，与肠神经系统和平滑肌层接触，但由于缺乏C-KIT^+细胞而损害了肠道自发收缩的ACK2处理的动物。具有有节奏的Ca^<2+> - 激活的Cl^传统。还发现，小肠的起搏器区域中的C-kit^+细胞从相同的Kit阳性前体细胞中发展起来，取决于动物体信号的程度。建议在电压钳条件下用咖啡因诱导的Ca^<2+>激活的k^+电流进行测试，并对细胞内Ca^<2+>浓度进行Fura-2荧光测量。总而言之，建议C-Kit在调节哺乳动物胃肠道功能的发展中起着重要作用。