Proliferation does not contribute to murine models of renin cell recruitment
Proliferation does not contribute to murine models of renin cell recruitment
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DOI：
10.1111/apha.13532
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发表时间：
2020-07-18
期刊：
影响因子：
--
通讯作者：
Gomez RA
中科院分区：
文献类型：
--
作者：
Guessoum O;Zainab M;Sequeira‐Lopez ML;Gomez RA
肾素细胞是调节血压和水-电解质平衡的重要细胞。在动态平衡受到威胁期间，肾脏中的肾素细胞数量增加，这一过程被称为募集。有人提出，招募是通过扩散发生的，但尚未进行系统的研究。我们试图确定扩散在多大程度上有助于招募工作。在分析肾素细胞的细胞周期之前，对小鼠进行了招募。对于急性威胁，我们让SV129和C57BL6小鼠接受低钠饮食和卡托普利。对处理小鼠的组织切片进行增殖标记物(Ki67、增殖细胞核抗原、PH3和BrdU)和肾素的联合染色。通过联合免疫组织化学染色和定期酸性席夫染色切片计数有丝分裂图形，研究了醛固酮合成酶和血管紧张素原缺失模型的慢性募集。最后，从招募的小鼠分离的肾素细胞的RNA-seq用于研究有丝分裂特征。服用低盐和卡托普利的小鼠显示肾素细胞数量增加(对照组为312±0.40，招募动物为692±0.85，P<；0.0001)，肾素信使核糖核酸增加10倍，循环肾素增加4倍。对这些肾脏切片进行增殖标记的联合染色显示，肾素细胞的增殖可以忽略不计(2%)，与对照组动物没有什么区别。同样，慢性招募模型--醛固酮合成酶KO和血管紧张素原KO--的增殖可以忽略不计。此外，与增殖细胞系相比，新招募的肾素细胞的转录组显示有丝分裂途径的整体下调。对动态平衡的急性和慢性生理威胁导致肾素合成细胞明显增加，但我们没有发现任何证据表明增殖参与其中。
Renin cells are essential for regulation of blood pressure and fluid‐electrolyte homeostasis. During homeostatic threat, the number of renin cells in the kidney increases, a process termed as recruitment. It has been proposed that recruitment occurs by proliferation, yet no systematic studies have been performed. We sought to determine the extent to which proliferation contributes to the recruitment process. Mice were subjected to recruitment before analysing the renin cells’ cell cycle. For acute threats, we subjected SV129 and C57Bl6 mice to a low sodium diet plus captopril. Tissue sections from treated mice were co‐stained for proliferation markers (Ki67, PCNA, pH3 and BrdU) and renin. Chronic recruitment was studied in deletion models of aldosterone synthase and angiotensinogen through co‐immunostaining and counting mitotic figures in periodic acid‐Schiff‐stained sections. Finally, RNA‐seq of renin cells isolated from recruited mice was performed to study mitotic signature. Mice subjected to low salt and captopril displayed increases in renin cell number (312 ± 40 in controls to 692 ± 85 in recruited animals, P<.0001), 10‐fold increases in renin mRNA and fourfold increases in circulating renin. Co‐staining these kidney sections for proliferation markers revealed negligible proliferation of renin cells (<2%), indistinguishable from control animals. Similarly, chronic models of recruitment—aldosterone synthase KO and angiotensinogen KO—had negligible proliferation. Additionally, the transcriptome of recruited renin cells revealed overall downregulation of mitotic pathways when compared to proliferative cell lines. Acute and chronic physiological threats to homeostasis produced a distinct increase in renin‐synthesizing cells, but we found no evidence to suggest the involvement of proliferation.
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影响因子：
4.8
作者：
Kim, HS;Maeda, N;Smithies, O
通讯作者：
Smithies, O
DOI：
10.1152/ajprenal.2001.281.2.f345
发表时间：
2001-08-01
影响因子：
4.2
作者：
Lopez, MLSS;Pentz, ES;Gomez, RA
通讯作者：
Gomez, RA
DOI：
10.1007/s00424-018-2118-z
发表时间：
2018-07
期刊：
Pflugers Archiv : European journal of physiology
影响因子：
--
作者：
Karger C;Machura K;Schneider A;Hugo C;Todorov VT;Kurtz A
通讯作者：
Kurtz A
影响因子：
8.3
作者：
Makhanova, Natalia;Sequeira-Lopez, Maria L. S.;Smithies, Oliver
通讯作者：
Smithies, Oliver
影响因子：
5.6
作者：
Lopez, Maria Luisa S. Sequeira;Gomez, R. Ariel
通讯作者：
Gomez, R. Ariel