The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells.
The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells.
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DOI：
10.1152/ajprenal.00559.2007
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Mathieson PW
中科院分区：
文献类型：
--
作者：
Saleem MA;Zavadil J;Bailly M;McGee K;Witherden IR;Pavenstadt H;Hsu H;Sanday J;Satchell SC;Lennon R;Ni L;Bottinger EP;Mundel P;Mathieson PW
肾小球足细胞是一种高度特化的细胞，具有超滤血液和支持肾小球毛细血管压力的能力。然而，人们对导致这种功能的遗传程序或最终的表型知之甚少。我们利用人类条件永生化细胞系探讨了这个问题，该细胞系从增殖的上皮表型分化为分化的形式。我们分析了分化过程中几个时间点的基因表达，并将受调控的基因分为主要功能类别。在分化过程中上调的一类新基因是与平滑肌相关的分子。我们进一步检测了平滑肌的表型，发现足细胞在体外和体内都一致地表达分化的平滑蛋白和钙粘蛋白以及特异的转录因子myocardin。足细胞对肾小球毛细血管的收缩作用是有争议的。我们使用了两种新的技术，当足细胞分化时，它们在体外强烈收缩，并实时证明血管紧张素II治疗减少了单层阻力，形态上与增强的收缩相关。我们认为，体外培养的成熟足细胞具有收缩平滑肌细胞的功能，其体内调节肾小球动力学和通透性的能力具有潜在的意义。
The glomerular podocyte is a highly specialized cell, with the ability to ultrafilter blood and support glomerular capillary pressures. However, little is known about either the genetic programs leading to this functionality or the final phenotype. We approached this question utilizing a human conditionally immortalized cell line, which differentiates from a proliferating epithelial phenotype to a differentiated form. We profiled gene expression during several time points during differentiation and grouped the regulated genes into major functional categories. A novel category of genes that was upregulated during differentiation was of smooth muscle-related molecules. We further examined the smooth muscle phenotype and showed that podocytes consistently express the differentiated smooth muscle markers smoothelin and calponin and the specific transcription factor myocardin, both in vitro and in vivo. The contractile contribution of the podocyte to the glomerular capillary is controversial. We demonstrated using two novel techniques that podocytes contract vigorously in vitro when differentiated and in real time were able to demonstrate that angiotensin II treatment decreases monolayer resistance, morphologically correlating with enhanced contractility. We conclude that the mature podocyte in vitro possesses functional apparatus of contractile smooth muscle cells, with potential implications for its in vivo ability to regulate glomerular dynamic and permeability characteristics.
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影响因子：
13.6
作者：
Coward, RJM;Foster, RR;Saleem, MA
通讯作者：
Saleem, MA
影响因子：
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--
作者：
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6
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通讯作者：
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