Sustained cell proliferation of renal epithelial cells in mice with inv mutation
Sustained cell proliferation of renal epithelial cells in mice with inv mutation
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DOI：
10.1111/j.1365-2443.2006.01011.x
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发表时间：
2006-10-01
期刊：
影响因子：
2.1
通讯作者：
Yokoyama, Takahiko
中科院分区：
文献类型：
--
作者：
Sugiyama, Noriyuki;Yokoyama, Takahiko
肾小管系统是肾单位的重要组成部分，肾单位是肾脏的结构和功能单位。肾小管扩张导致肾囊肿。肾囊性疾病的遗传形式表明肾小管的大小是由遗传决定的。 inv被发现是一种具有肾囊肿和逆位的突变体。 Inv/inv、inv Delta C::GFP (inv Delta C) 小鼠是通过将缺乏 C 末端的 inv 基因 (inv Delta C) 引入 inv/inv 小鼠而产生的。小鼠出现多个肾囊肿，但没有位置异常，这为我们研究肾小管结构维护中的 inv 功能提供了机会。在本研究中，我们发现 inv 以剂量依赖性方式抑制囊肿进展，并且 inv Delta C 囊性肾显示细胞增殖和凋亡增加。 G1-S 进程的细胞周期调节因子在囊性肾中被激活。此外，cDNA 微阵列和半定量 RT-PCR 分析显示，4 周龄时，生长相关基因在囊性肾中保持高水平表达，而在对照肾中表达减少，表明 inv Delta C 肾中的细胞在细胞周期中仍然活跃。 inv 蛋白的功能之一可能为肾上皮细胞增殖提供停止信号。
A tubule system is an important component of the nephron, which is the structural and functional unit of the kidney. Expansion of renal tubules results in renal cysts. Hereditary forms of renal cystic diseases suggest that tubular size is determined genetically. The inv was discovered as a mutant with renal cysts and situs inversus. Inv/inv, inv Delta C::GFP (inv Delta C) mouse was created by the introduction of the inv gene lacking the C-terminus (inv Delta C) into inv/inv mice. The mouse develops multiple renal cysts without situs abnormality, giving us an opportunity to study inv function in renal tubular structure maintenance. In the present study, we showed that inv suppresses cyst progression in a dose-dependent manner and that the inv Delta C cystic kidneys showed increased cell proliferation and apoptosis. Cell cycle regulators for G1-S progression were activated in the cystic kidney. Furthermore, cDNA microarray and semiquantitative RT-PCR analysis showed that growth-related genes maintained a high level of expression in the cystic kidney at 4 weeks of age whereas they were decreased in control kidneys, suggesting that cells in inv Delta C kidney are still active in the cell cycle. One of the inv protein functions may provide a stop signal for renal epithelial cell proliferation.