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首页> 外文期刊>American Journal of Physiology >Altered expression of selected genes in kidney of rats with lithium-induced NDI.
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Altered expression of selected genes in kidney of rats with lithium-induced NDI.

机译：锂诱导的NDI大鼠肾脏中所选基因的表达改变。

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摘要

Lithium treatment is associated with development of nephrogenic diabetes insipidus, caused in part by downregulation of collecting duct aquaporin-2 (AQP2) and AQP3 expression. In the present study, we carried out cDNA microarray screening of gene expression in the inner medulla (IM) of lithium-treated and control rats, and selected genes were then investigated at the protein level by immunoblotting and/or immunohistochemistry. The following genes exhibited significantly altered transcription and mRNA expression levels, and these were compatible with the changes in protein expression. 11beta-Hydroxysteroid dehydrogenase type 2 protein expression in the IM was markedly increased (198 +/- 25% of controls, n = 6), and immunocytochemistry demonstrated an increased labeling of IM collecting duct (IMCD) principal cells. This indicated altered renal mineralocorticoid/glucocorticoid responses in lithium-treated rats. The inhibitor of cyclin-dependent kinases p27 (KIP) protein expression was significantly decreased or undetectable in the IMCD cells, pointing to increased cellular proliferation and remodeling. Heat shock protein 27 protein expression was decreased in the IM (64 +/- 6% of controls, n = 6), likely to be associated with the decreased medullary osmolality in lithium-treated rats. Consistent with this, lens aldose reductase protein expression was markedly decreased in the IM (16 +/- 2% of controls, n = 6), and immunocytochemistry revealed decreased expression in the thin limb cells in the middle and terminal parts of the IM. Ezrin protein expression was upregulated in the IM (158 +/- 16% of controls, n = 6), where it was predominantly expressed in the apical and cytoplasmic domain of the IMCD cells. Increased ezrin expression indicated remodeling of the actin cytoskeleton and/or altered regulation of IMCD transporters. In conclusion, the present study demonstrates changes in gene expression not only in the collecting duct but also in the thin limb of the loop of Henle in the IM, and several of thesegenes are linked to altered sodium and water reabsorption, cell cycling, and changes in interstitial osmolality.
机译：锂治疗与肾病性尿崩症的发展有关，这部分是由于收集导管水通道蛋白2（AQP2）和AQP3表达的下调引起的。在本研究中，我们进行了cDNA微阵列筛选，对锂处理和对照组大鼠的髓质（IM）中的基因表达进行了筛选，然后通过免疫印迹和/或免疫组化在蛋白质水平上研究了选定的基因。以下基因表现出显着改变的转录和mRNA表达水平，并且与蛋白质表达的变化兼容。 IM中的11beta-羟基类固醇脱氢酶2型蛋白表达显着增加（对照组的198 +/- 25％，n = 6），并且免疫细胞化学显示IM收集导管（IMCD）主细胞的标记增加。这表明在锂治疗的大鼠中肾盐皮质激素/糖皮质激素反应改变。细胞周期蛋白依赖性激酶p27（KIP）蛋白表达的抑制剂在IMCD细胞中显着降低或无法检测到，表明细胞增殖和重塑增加。 IM中热休克蛋白27蛋白表达降低（对照组的64 +/- 6％，n = 6），这可能与锂治疗大鼠的髓质渗透压降低有关。与此相一致，晶状体醛糖还原酶蛋白的表达在IM中显着降低（对照组的16 +/- 2％，n = 6），免疫细胞化学显示IM中部和末梢的薄肢细胞表达降低。 Ezrin蛋白表达在IM中上调（对照组的158 +/- 16％，n = 6），其中主要在IMCD细胞的顶端和胞质域中表达。 ezrin表达增加表明肌动蛋白细胞骨架重塑和/或IMCD转运蛋白的调节改变。总之，本研究表明IM中不仅在收集管中而且在Henle环的薄肢中基因表达均发生变化，并且这些基因中的几个与钠和水的重吸收改变，细胞周期变化有关。间质渗透压。

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