CYCLOOXYGENASE-2 IS ASSOCIATED WITH THE MACULA DENSA OF RAT-KIDNEY AND INCREASES WITH SALT RESTRICTION
CYCLOOXYGENASE-2 IS ASSOCIATED WITH THE MACULA DENSA OF RAT-KIDNEY AND INCREASES WITH SALT RESTRICTION
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DOI：
10.1172/jci117620
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发表时间：
1994-12-01
影响因子：
15.9
通讯作者：
BREYER, MD
中科院分区：
文献类型：
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作者：
HARRIS, RC;MCKANNA, JA;BREYER, MD
肾脏是前列腺素的丰富来源。这些类二十烷化合物是由花生四烯酸的环氧化酶依赖性代谢形成的，是肾小球血流动力学和小管钠和水重吸收的重要生理介质。目前已鉴定出环氧化酶（COX）的两种不同的同工异构体：由2.8 kb mRNA编码的组成型COX-1和由4.0-4.5 kb mRNA编码的有丝分裂原激活型COX-2。COX-2的表达在发育和炎症过程中增加，但除大脑外，组成表达较低。人们普遍认为，前列腺素的生理性肾脏生成是由COX-1介导的，然而，在没有炎症的情况下，肾脏中也可检测到低水平的COX-2 mRNA。为了研究COX-2在肾脏中的作用并确定其在肾内的定位，我们使用了针对大鼠COX-2的3'非翻译区和COX-2特异性抗血清的1.3 kb cDNA探针。cox -2特异性cDNA探针与成年大鼠肾脏总RNA中4.4 kb的转录物杂交。从肾皮质和乳头分离的微粒体的免疫印迹显示两个部位的COX-2免疫反应。原位杂交和免疫组化结果显示，肾皮质COX-2的表达定位于肾小球旁器的黄斑致密区和Henle皮质厚升肢的邻近上皮细胞。此外，在乳头间质细胞中检测到COX-2的免疫反应性。在小动脉、肾小球、皮质或髓质收集管中未检测到COX-2信息或免疫反应蛋白。当动物长期限钠时，黄斑致密区COX-2水平增加3倍（从0.86+/-0.08增加到2.521+/-0.43/mm(2)），皮层COX-2免疫反应细胞总面积从34 μ m(2)/mm(2)增加到226 μ m(2)/mm(2)。COX-2的肾内分布及其在钠限制下的表达增加表明，该酶除了在炎症和生长反应中发挥作用外，还可能在调节盐、容量和血压稳态中发挥重要作用。
The kidney is a rich source of prostaglandins. These eicosanoids, formed by cyclooxygenase-dependent metabolism of arachidonic acid, are important physiologic mediators of renal glomerular hemodynamics and tubular sodium and water reabsorption. Two separate isoforms of cyclooxygenase (COX) have now been identified: constitutive COX-1, encoded by a 2.8-kb mRNA, and mitogen-activated COX-2, encoded by a 4.0-4.5-kb mRNA. COX-2 expression increases during development and inflammation, but, except for brain, constitutive expression is low. It has been generally accepted that physiologic renal production of prostaglandins is mediated by COX-1, However, in the absence of inflammation, low levels of COX-2 mRNA are also detectable in the kidney. To examine the role of COX-2 in the kidney and determine its intrarenal localization, we used a 1.3-kb cDNA probe specific for the 3' untranslated region of rat COX-2 and COX-2-specific antiserum. The COX-2-specific cDNA probe hybridized with a 4.4-kb transcript in total RNA from adult rat kidney. Immunoblots of microsomes isolated from kidney cortex and papilla indicated immunoreactive COX-2 in both locations. In situ hybridization and immunohistochemistry indicated that renal cortical COX-2 expression was localized to the macula densa of the juxtaglomerular apparatus and to adjacent epithelial cells of the cortical thick ascending limb of Henle. In addition, COX-2 immunoreactivity was detected in interstitial cells in the papilla. No COX-2 message or immunoreactive protein was detected in arterioles, glomeruli, or cortical or medullary collecting ducts.When animals were chronically sodium restricted, the level of COX-2 in the region of the macula densa increased threefold (from 0.86+/-0.08 to 2.521+/-0.43/mm(2)) and the total area of the COX-2 immunoreactive cells in cortex increased from 34 mu m(2)/mm(2) of cortex to 226 mu m(2)/mm(2) of cortex. The intrarenal distribution of COX-2 and its increased expression in response to sodium restriction suggest that in addition to its proposed role in inflammatory and growth responses, this enzyme may play an important role in the regulation of salt, volume, and blood pressure homeostasis.