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Research on the development of biopacemaker by use of plnipotent P19CL6 cells.

利用多能P19CL6细胞开发生物起搏器的研究。

基本信息

批准号：
17590755
负责人：
ONO Katsushige
金额：
$ 1.47万
依托单位：
Oita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590755/
关键词：
cardio : myocyte differentiation regeneration pacemaker cell transplantation

项目摘要

Ttranscription factors on heart differentiation and cell growth factors are identified in sequence by recent molecular biology studies, and elucidating mechanism of cardiac muscle cell differentiation. Differentiation of a cardiac muscle cell is induced by cell growth factors such as BMP and ET-1, and specific transcription factors (Csx/Nkx-2.5, GATA4, MEF2C) are activated. Then cardiac muscle cell specific protein (myosin, actin, an ion channel) finally develops. However, a specific transcription factor that is to control manifestation of cardiac ion channels is not yet elucidated. In addition, the details of ion channel manifestation as a trigger for action potentials by means of myocardial excitation-contraction coupling are not clear. On the other hand, MAPK is a main signal conveying extracellular information to cellular signals via actions of MAPKKK and MAPKK, which are related to cell differentiation and development. We analyzed transcription factors to go through a signal in a … More cell concerned with current build-up in a differentiated cardiac muscle cell derived from pluripotent P19CL6 cells. P19CL6 cells developed into cardiac cells by dimethyl sulfoxide (DMSO) and acquires automaticity. It is known that mitogen-activated protein kinase (MAPK) plays an important role in cardiac muscle cell differentiation and morphogenesis. We reviewed a signal in the cell which affected the membrane current formation in a P19CL6 cell origin-cardiac muscle cell, ion channel manifestation, in particular, to go through MAPK by this study. A P19CL6 cell expresses hyperpolarization elicitation influx (Ih) channel and two kinds of Ca channels (I_<Ca. L>, I_<Ca. T>) after differentiated and shows automaticity of 89 bpm. As for the automatic beat and pacemaker ion channel after differentiation, cellular development was halted by inhibition of p38-MAPK, and action potential configuration was undeveloped from undifferentiated P19CL6 cells. Furthermore, transcription factor GATA4 was highly restrained. On the other hand, myocytes under infibition of classic MAPK (ERK1/2,5) and JNK showed automatic of 83-108 bpm, and three kinds of pacemaker ion channels were observed. Therefore, it is suggested that signals which go through nonclassical MAPK or p38-MAPK are was concerned with manifestation of developing pacemaker ion channels in differentiation stage to a cardiac muscle derived from P19CL6 cells. It may identify a potential theory of the bio-pacemaker which controls ion channel expression in targeted myocytes. Therefore, intervention of transcription factor Csx/Nkx2.5 becomes a potential target to identify the mechanism for ion channel expression and maturation. Less

近年来的分子生物学研究对心肌细胞分化的转录因子和细胞生长因子进行了序列鉴定，阐明了心肌细胞分化的机制。心肌细胞的分化由细胞生长因子如BMP和ET-1诱导，并且特异性转录因子（Csx/Nkx-2.5、GATA 4、MEF 2C）被激活。然后，心肌细胞特异性蛋白质（肌球蛋白，肌动蛋白，离子通道）最终发展。然而，控制心脏离子通道表现的特定转录因子尚未阐明。此外，离子通道通过心肌兴奋-收缩偶联触发动作电位的细节尚不清楚。另一方面，MAPK是通过与细胞分化和发育相关的MAPKKK和MAPKK作用将细胞外信息传递到细胞内的主要信号。我们分析了转录因子， ...更多信息细胞，其与源自多能P19 CL 6细胞的分化心肌细胞中的电流积聚有关。P19 CL 6细胞经二甲基亚砜（DMSO）诱导分化为心肌细胞，并获得自律性。已知丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）在心肌细胞分化和形态发生中起重要作用。本文综述了P19 CL 6细胞来源的心肌细胞中影响膜电流形成的细胞内信号，特别是通过MAPK的离子通道表现。P19 CL 6细胞分化后表达超极化激发内流（Ih）通道和两种钙通道（I_<Ca. L>，I_<Ca. T>），自律性为89 bpm。分化后的P19 CL 6细胞，由于p38-MAPK的抑制，细胞发育停止，动作电位构型不发育。此外，转录因子GATA 4受到高度抑制。而经典MAPK（ERK 1/2，5）和JNK作用下的心肌细胞则表现出83-108次/min的自律性，并观察到三种起搏离子通道。因此，认为通过非经典MAPK或p38-MAPK的信号与向来自P19 CL 6细胞的心肌分化阶段发育的起搏离子通道的表现有关。这可能会确定一个潜在的理论生物起搏器控制离子通道的表达在靶向心肌细胞。因此，转录因子Csx/Nkx2.5的干预成为鉴定离子通道表达和成熟机制的潜在靶点。少