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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 是一种受体型酪氨酸激酶，可以调节哺乳动物胃肠道平滑肌组织的发育。为了说明 c-kit 如何在平滑肌组织的功能发育中发挥作用，我们调查了腹腔注射中和性抗 c-kit 单克隆抗体 (ACK2) 8 个月的 BALB/c 小鼠发育中胃肠道中 c-kit 阳性 (c-kit^+) 细胞（即 Cajal 间质细胞）的数量和功能变化。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，但在ACK2处理的动物中却没有，这些动物由于缺乏c-kit^+细胞而损害了肠道的自发收缩力。其具有节律性Ca ^ 2+ -激活的Cl ^ -电导。还发现小肠起搏器区域中的c-kit^+细胞和纵向平滑肌细胞由相同的kit阳性前体细胞发育而来，这取决于kit信号的程度。在从ACK2处理的动物的胃肠道分离的平滑肌细胞中，细胞质中的兰尼碱敏感的Ca^2+储存功能障碍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，并用fura-2荧光测量细胞内Ca^2+浓度。总而言之，表明c-kit在调节哺乳动物胃肠道功能的发育中发挥重要作用。