Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration.
Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration.
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DOI：
10.1002/path.4125
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发表时间：
2013-04
影响因子：
7.3
通讯作者：
Moeller, Marcus J.
中科院分区：
文献类型：
--
作者：
Smeets, Bart;Boor, Peter;Dijkman, Henry;Sharma, Shagun V.;Jirak, Peggy;Mooren, Fieke;Berger, Katja;Bornemann, Joerg;Gelman, Irwin H.;Floege, Juergen;van der Vlag, Johan;Wetzels, Jack F. M.;Moeller, Marcus J.
急性肾小管坏死后，受损的肾小管细胞再生主要来自内在肾细胞。这可能发生于预先存在的小管内干/祖细胞群或任何存活的近端小管细胞。在这项研究中，我们的特点是CD 24-，CD 133-，波形蛋白阳性细胞亚群分散在整个近端小管在正常人肾脏。与相邻的“正常”近端肾小管细胞相比，这些CD 24阳性细胞含有较少的细胞质，较少的线粒体，没有刷状缘。此外，描述了49种标记蛋白，其在近端小管内以类似的分散模式表达。对于这些标志物中的8个，我们证实了与CD 24的共定位。在急性肾小管坏死（ATN）患者的人类活检中，CD 24阳性肾小管细胞的数量增加。在正常人肾脏和ATN活检中，约85%的增殖细胞为CD 24阳性-表明该细胞群参与肾小管再生。在健康大鼠肾脏中，不存在新的细胞亚群。然而，在单侧输尿管梗阻（UUO）时，在损伤的肾脏中检测到大量的新细胞群。总之，在人肾活检中，CD 24阳性细胞代表具有异常表型的肾小管细胞，其特征在于独特的形态学和标志物表达。在急性肾小管损伤后，这些细胞变得更多。在健康的大鼠肾脏中，这些细胞是不可检测的，而在UUO后，它们重新出现-反对这些细胞代表预先存在的祖细胞群体的观点。我们的数据表明，而这些细胞代表参与再生的瞬时去分化的肾小管细胞。
Regeneration of injured tubular cells occurs after acute tubular necrosis primarily from intrinsic renal cells. This may occur from a pre-existing intratubular stem/progenitor cell population or from any surviving proximal tubular cell. In this study, we characterize a CD24-, CD133-, and vimentin-positive subpopulation of cells scattered throughout the proximal tubule in normal human kidney. Compared to adjacent ‘normal’ proximal tubular cells, these CD24-positive cells contained less cytoplasm, fewer mitochondria, and no brush border. In addition, 49 marker proteins are described that are expressed within the proximal tubules in a similar scattered pattern. For eight of these markers, we confirmed co-localization with CD24. In human biopsies of patients with acute tubular necrosis (ATN), the number of CD24-positive tubular cells was increased. In both normal human kidneys and the ATN biopsies, around 85% of proliferating cells were CD24-positive – indicating that this cell population participates in tubular regeneration. In healthy rat kidneys, the novel cell subpopulation was absent. However, upon unilateral ureteral obstruction (UUO), the novel cell population was detected in significant amounts in the injured kidney. In summary, in human renal biopsies, the CD24-positive cells represent tubular cells with a deviant phenotype, characterized by a distinct morphology and marker expression. After acute tubular injury, these cells become more numerous. In healthy rat kidneys, these cells are not detectable, whereas after UUO, they appeared de novo – arguing against the notion that these cells represent a pre-existing progenitor cell population. Our data indicate rather that these cells represent transiently dedifferentiated tubular cells involved in regeneration.
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影响因子：
3.7
作者：
Griguer CE;Oliva CR;Gobin E;Marcorelles P;Benos DJ;Lancaster JR Jr;Gillespie GY
通讯作者：
Gillespie GY
影响因子：
5.2
作者：
Angelotti, Maria Lucia;Ronconi, Elisa;Romagnani, Paola
通讯作者：
Romagnani, Paola
影响因子：
5
作者：
Burnworth, Bettina;Pippin, Jeff;Nelson, Peter J.
通讯作者：
Nelson, Peter J.
影响因子：
19.6
作者：
Cheng, CW;Rifai, A;Chen, A
通讯作者：
Chen, A
影响因子：
13.6
作者：
Langworthy, Melissa;Zhou, Bin;Baldwin, H. Scott
通讯作者：
Baldwin, H. Scott