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The mechanisms involved in the regulation of mmesangial cell phenotype by endothetial cells : role of gap junction

内皮细胞调节系膜细胞表型的机制：间隙连接的作用

基本信息

批准号：
15590845
负责人：
YAO Jian
金额：
$ 2.3万
依托单位：
University of Yamanashi
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 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590845/
关键词：
Mesangial cells Gap junction Connexin43 Endothelial cells Nitric oxide Phosphodiesterase 3 Protein kinase A Calcium protein kinaseA 糸球体

项目摘要

One of intriguing features of mesangial cells (MCs) is their extraordinary abundance in gap junctions (GJs). However, information about the functional role of GJs in glomerular cells is still lacking. Our studies were designed to address this question. Our findings can be summarized as followings. 1. MCs are coupled by functional GJ channels. MCs were demonstrated to express GJ protein Cx43 and exhibited functional GJIC as assessed by dye-transfer assay. 2. GJ mediates the transmission of intercellular signal. Mechanical stimulation of a single MC initiated a rise in Ca^<2+> in the stimulated cells, which was followed by transmission of the signal to surrounding cells. The spreading of the Ca^<2+> signal in MCs was completely prevented by GJ inhibitors. 3. Regulation of MC phenotypes by glomerular endothelial cells via GJs. Using cultured human glomerular cells, endothelial cells were demonstrated to express GJ proteins including Cx43, Cx40 and Cx37, and GJ, which was functional, as as … More sessed by dye-transfer assay. Ultrastructural study revealed that presence of GJ protein Cx43 between endothelial cells and MCs. GJ might participates in the endothelial-mediated regulation of MC functions. 4. Regulation of GJ by endothelial-derived vasodilative factor nitric oxide (NO). Endothelial derived vasodiative factor, nitric oxide (NO), was identified to be a potent stimulator of Cx43 expression and functional gap junctional intercellular communication (GJIC) in MCs. This action of NO was shown to be due to the activation of protein kinase A via cGMP-dependent inhibition of phosphodiesterase 3 (PDE3). This finding may open a new window toward our further understanding of the vascular role of NO under various pathophysiologic situations. In conclusion, several lines of evidence support the important roles of GJs in MC functions. (1) MCs are extensively connected by functional GJs. (2) GJs in MCs participate in the regulation of important physiological processes, including tubuloglomerular feedback and glomerular filtration. (3) Factors critically involved in various processes of glomerular pathophysiology are potent regulators of Cx43 expression and GJIC in MCs. These data suggest that GJs may participate in glomerular pathophysiology. Less

系膜细胞 (MC) 的一个有趣特征是其间隙连接 (GJ) 异常丰富。然而，关于 GJ 在肾小球细胞中的功能作用的信息仍然缺乏。我们的研究旨在解决这个问题。我们的研究结果可总结如下。 1. MC 通过功能性 GJ 通道耦合。 MCs 被证明表达 GJ 蛋白 Cx43，并通过染料转移测定评估显示出功能性 GJIC。 2. GJ介导细胞间信号的传递。单个MC的机械刺激引起受刺激细胞中Ca 2+ 的升高，随后将信号传输至周围细胞。 GJ抑制剂完全阻止了MC中Ca 2+ 信号的传播。 3. 肾小球内皮细胞通过 GJ 对 MC 表型的调节。使用培养的人肾小球细胞，内皮细胞被证明可以表达 GJ 蛋白，包括 Cx43、Cx40 和 Cx37，并且通过染料转移测定，GJ 具有功能性。超微结构研究表明内皮细胞和 MC 之间存在 GJ 蛋白 Cx43。 GJ 可能参与内皮介导的 MC 功能调节。 4.内皮源性血管舒张因子一氧化氮（NO）对GJ的调节。内皮衍生的血管舒张因子一氧化氮 (NO) 被认为是 MC 中 Cx43 表达和功能性间隙连接细胞间通讯 (GJIC) 的有效刺激剂。 NO 的这种作用被证明是由于通过 cGMP 依赖性磷酸二酯酶 3 (PDE3) 抑制激活蛋白激酶 A。这一发现可能为我们进一步了解 NO 在各种病理生理情况下的血管作用打开一扇新的窗口。总之，多种证据支持 GJ 在 MC 功能中的重要作用。 (1) MC之间通过功能GJ广泛连接。 (2)MCs中的GJ参与重要生理过程的调节，包括肾小管肾小球反馈和肾小球滤过。 (3) 与肾小球病理生理学各个过程密切相关的因素是 MC 中 Cx43 表达和 GJIC 的有效调节因子。这些数据表明 GJ 可能参与肾小球病理生理学。较少的