AN OSMOTICALLY TOLERANT INNER MEDULLARY COLLECTING DUCT CELL-LINE FROM AN SV40 TRANSGENIC MOUSE

AN OSMOTICALLY TOLERANT INNER MEDULLARY COLLECTING DUCT CELL-LINE FROM AN SV40 TRANSGENIC MOUSE
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DOI:
10.1152/ajprenal.1993.265.3.f416
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发表时间:
1993-09-01
影响因子:
--
通讯作者:
GULLANS, SR
GULLANS, SR
中科院分区:
其他
文献类型:
--
作者:
RAUCHMAN, MI;NIGAM, SK;GULLANS, SR

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终末内髓集合管(IMCD)在决定最终尿液成分中起重要作用。目前,还没有从这段肾单位衍生出的连续细胞系。我们从针对猴病毒SV40(大T抗原)早期区域的转基因小鼠的IMCD末端建立了一株细胞系。该细胞系mIMCD-3保留了肾单位段的许多分化特征,包括高跨上皮阻力(1,368+/-172 Omega·cm2),阿米洛利(41+/-7%)和心钠素(40+/-9%)抑制心尖到基础钠流量,Western印迹分析表明存在对阿米洛利敏感的钠通道,以及对高渗应激反应主要有机渗透压的积累。值得注意的是,mIMCD-3细胞适应能力强,能够在添加高渗盐和尿素的高渗介质中生长,最高可达910molmoL/kgH2O。这些极端的渗透条件存在于体内的肾髓质中,但已知对大多数其他细胞是致命的。该细胞系对研究细胞对渗透胁迫的适应性以及肾单位段的细胞生物学和运输生理学具有重要意义。
The terminal inner medullary collecting duct (IMCD) plays an important role in determining the final urinary composition. Currently, there is no continuous cell line derived from this nephron segment. We have developed a cell line derived from the terminal IMCD of mice transgenic for the early region of simian virus SV40 (large T antigen). This cell line, mIMCD-3, retains many differentiated characteristics of this nephron segment including high transepithelial resistance (1,368 +/- 172 OMEGA.cm2), inhibition of apical-to-basal sodium flux by amiloride (41 +/- 7%) and by atrial natriuretic peptide (ANP) (40 +/- 9%), the presence of the amiloride-sensitive sodium channel as determined by Western blot analysis, and accumulation of the major organic osmolytes in response to hypertonic stress. Significantly, mIMCD-3 cells adapted readily and were able to grow in hypertonic medium supplemented with NaCl and urea up to 910 mosmol/kgH2O. These extreme osmotic conditions exist in the renal medulla in vivo but are known to be lethal to most other cells. This cell line should be highly useful for the study of the cellular adaptation to osmotic stress and the cell biology and transport physiology of this nephron segment.