Regulation of cyclooxygenase expression in the kidney by dietary salt intake.
Regulation of cyclooxygenase expression in the kidney by dietary salt intake.
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DOI：
10.1152/ajprenal.1998.274.3.f481
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发表时间：
1998-03
期刊：
影响因子：
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通讯作者：
Tianxin Yang;I. Singh;H. Pham;Daqing Sun;A. Smart;J. Schnermann;J. Briggs
中科院分区：
文献类型：
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作者：
Tianxin Yang;I. Singh;H. Pham;Daqing Sun;A. Smart;J. Schnermann;J. Briggs
本研究旨在确定膳食盐摄入量对肾环加氧酶-1 (COX-1) 和-2 (COX-2) 表达的影响。通过蛋白质印迹法评估蛋白质水平，并通过逆转录聚合酶链反应（RT-PCR）对从肾区域、解剖的肾单位片段和培养的肾细胞制备的cDNA评估mRNA表达。两种同工型在内髓质 (IM) 中均高水平表达，而在外髓质和皮质中检测到低水平。 COX-1 mRNA 存在于肾小球和整个集合管中，而 COX-2 mRNA 仅限于包含致密斑的段 (MD)、皮质厚升肢 (CTAL)，并且在内髓集合管中的水平显着较低。两种亚型在培养的髓质间质细胞中均以高水平表达，而在原代系膜细胞和集合管细胞系中以较低水平表达。维持大鼠低或高 NaCl 饮食 1 周并不影响 COX-1 的表达。在接受高盐饮食治疗的大鼠 IM 中，COX-2 mRNA 增加了 4.5 倍，蛋白质水平增加了 9.5 倍。相比之下，高盐饮食的大鼠皮质COX-2 mRNA水平下降2.9倍，低盐饮食的大鼠皮质COX-2 mRNA水平增加3.3倍。低盐饮食使 MD 中的 COX-2 mRNA 增加了 7.7 倍，在 CTAL 中增加了 3.3 倍。膳食盐对皮层和髓质中COX-2的不同调节表明，不同肾脏区域的前列腺素具有不同的功能，髓质的产生在容量超负荷时发挥促进盐和水的排泄的作用，而皮质前列腺素可以在容量不足时保护肾小球循环。
The present studies were undertaken to determine the effect of dietary salt intake on the renal expression of cyclooxygenase-1 (COX-1) and -2 (COX-2). Protein levels were assessed by Western blotting, and mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) on cDNA prepared from kidney regions, dissected nephron segments, and cultured renal cells. Both isoforms were expressed at high levels in inner medulla (IM), with low levels detected in outer medulla and cortex. COX-1 mRNA was present in the glomerulus and all along the collecting duct, whereas COX-2 mRNA was restricted to the macula densa-containing segment (MD), cortical thick ascending limb (CTAL), and, at significantly lower levels, in the inner medullary collecting duct. Both isoforms were highly expressed at high levels in cultured medullary interstitial cells and at lower levels in primary mesangial cells and collecting duct cell lines. Maintaining rats on a low- or high-NaCl diet for 1 wk did not affect expression of COX-1. In IM of rats treated with a high-salt diet, COX-2 mRNA increased 4.5-fold, and protein levels increased 9.5-fold. In contrast, cortical COX-2 mRNA levels decreased 2.9-fold in rats on a high-salt diet and increased 3.3-fold in rats on a low-salt diet. A low-salt diet increased COX-2 mRNA 7.7-fold in MD and 3.3-fold in CTAL. Divergent regulation of COX-2 in cortex and medulla by dietary salt suggests that prostaglandins in different kidney regions serve different functions, with medullary production playing a role in promoting the excretion of salt and water in volume overload, whereas cortical prostaglandins may protect glomerular circulation in volume depletion.