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

肾小球系膜细胞的一个有趣的特征是其异常丰富的缝隙连接。然而，关于GJs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。我们的研究结果可以总结如下。1. MC通过功能性GJ通道偶联。MC被证明表达GJ蛋白Cx43，并表现出功能性GJIC通过染料转移试验进行评估。2. GJ介导细胞间信号的传递。对单个MC进行机械刺激可使受刺激细胞中的Ca^<2+>升高，随后将信号传递到周围细胞。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调节MC表型。使用培养的人肾小球细胞，证明内皮细胞表达GJ蛋白，包括Cx43、Cx40和Cx37，以及功能性的GJ，如 关于我们 通过染料转移测定法测定。超微结构显示内皮细胞和MC之间存在GJ蛋白Cx43。GJ可能参与内皮细胞对MC功能的调节。4.内皮源性血管舒张因子一氧化氮（NO）对GJ的调节。内皮源性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）的有效刺激物。NO的这种作用被证明是由于通过cGMP依赖性抑制磷酸二酯酶3（PDE 3）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了一个新的窗口。总之，有几条证据支持GJs在MC功能中的重要作用。(1)MC与功能性GJ广泛连接。(2)MC中的GJ参与重要的生理过程的调节，包括管球反馈和肾小球滤过。(3)关键参与肾小球病理生理学的各种过程的因素是MC中Cx43表达和GJIC的有效调节剂。这些数据表明，GJs可能参与肾小球病理生理。少

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