Sugiyama Noriyuki, Yokoyama Takahiko
Department of Anatomy and Developmental Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Genes Cells. 2006 Oct;11(10):1213-24. doi: 10.1111/j.1365-2443.2006.01011.x.
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 deltaC::GFP (inv deltaC) mouse was created by the introduction of the inv gene lacking the C-terminus (inv deltaC) 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 deltaC 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 deltaC kidney are still active in the cell cycle. One of the inv protein functions may provide a stop signal for renal epithelial cell proliferation.
肾小管系统是肾单位的重要组成部分，而肾单位是肾脏的结构和功能单位。肾小管扩张会导致肾囊肿。遗传性肾囊性疾病表明肾小管大小由基因决定。inv最初是作为一种伴有肾囊肿和内脏反位的突变体被发现的。通过将缺失C末端的inv基因（inv deltaC）导入inv/inv小鼠中，培育出了Inv/inv、inv deltaC::GFP（inv deltaC）小鼠。该小鼠会出现多个肾囊肿但无内脏位置异常，这为我们研究inv在维持肾小管结构中的功能提供了契机。在本研究中，我们发现inv以剂量依赖的方式抑制囊肿进展，并且inv deltaC肾囊肿的肾脏显示细胞增殖和凋亡增加。参与G1-S期进展的细胞周期调节因子在囊性肾脏中被激活。此外，cDNA微阵列和半定量RT-PCR分析表明，与生长相关的基因在4周龄的囊性肾脏中保持高水平表达，而在对照肾脏中则降低，这表明inv deltaC肾脏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一个终止信号。
