Necas E, Ponka P
Charles University, Prague, Czech Republic.
Eur J Clin Invest. 1998 Nov;28(11):918-23. doi: 10.1046/j.1365-2362.1998.00389.x.
The erythropoietin (EPO) gene is activated in peritubular cells of the renal cortex in response to hypoxia and EPO is secreted into the circulation. Oxygen tension in the venous blood normally determine EPO elaboration, and, therefore, oxygen consumption in the kidney appears to be an essential part of the oxygen-sensing physiological mechanism. As renal oxygen consumption is closely linked to urine production, we have compared responsiveness of the EPO gene to diminished oxygen supply in the normal kidney with that of the hydronephrotic kidney, resulting from ureter ligation.
Erythropoietin mRNA was determined in RNA extracted from murine kidneys at various times up to 61 days after ureter ligation. Mice were exposed to hypoxia for 4 h before being killed.
Unilateral ureter ligation significantly decreased EPO mRNA levels in the affected kidney. However, the ability to increase EPO mRNA recovered between days 4 and 22, despite persisting ureter ligation.
Our results demonstrate a dissociation between the excretory functions of the kidney and EPO production. Moreover, they show an early but transient suppression of EPO gene responsiveness to hypoxia after ureter ligation.
促红细胞生成素(EPO)基因在肾皮质的肾小管周围细胞中因缺氧而被激活,EPO分泌入血液循环。静脉血中的氧张力通常决定EPO的生成,因此,肾脏的氧消耗似乎是氧感应生理机制的重要组成部分。由于肾脏的氧消耗与尿液生成密切相关,我们比较了正常肾脏和因输尿管结扎导致的肾积水肾脏中EPO基因对氧供应减少的反应性。
在输尿管结扎后长达61天的不同时间,测定从小鼠肾脏提取的RNA中的促红细胞生成素mRNA。在处死小鼠前,使其暴露于低氧环境4小时。
单侧输尿管结扎显著降低了患侧肾脏中EPO mRNA水平。然而,尽管输尿管结扎持续存在,但在第4天至第22天之间,增加EPO mRNA的能力恢复了。
我们的结果表明肾脏的排泄功能与EPO产生之间存在分离。此外,它们显示输尿管结扎后EPO基因对缺氧的反应性有早期但短暂的抑制。