Flow-induced prostaglandin E2 release regulates Na and K transport in the collecting duct
Flow-induced prostaglandin E2 release regulates Na and K transport in the collecting duct
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DOI：
10.1152/ajprenal.00169.2012
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Rohatgi, Rajeev
中科院分区：
文献类型：
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作者：
Flores, Daniel;Liu, Yu;Rohatgi, Rajeev
弗洛雷斯D，刘Y，刘W，Satlin LM，Rohatgi R.流动诱导的前列腺素E-2释放调节集合管中的Na和K转运。美国肾脏生理学杂志303：F632-F638，2012年。首次发表于2012年6月13日; doi：10.1152/ajprenal.00169.2012.-流体剪切应力（FSS）是阳离子在集合管（CD）中运输的关键调节器。高饮食钠（Na）消耗增加尿流量，Na排泄和前列腺素E-2（PGE（2））排泄。我们假设，增加肾小管流速引起的FSS增加诱导PGE（2）从肾上皮细胞释放到细胞外室并调节离子转运。从暴露于生理水平的FSS的CD细胞回收的培养基显示与静态对照相比几倍高的PGE（2）浓度。在暴露于FSS期间，用环氧合酶-1（考克斯-1）或考克斯-2抑制剂处理CD细胞，在相同程度上限制了PGE（2）浓度的增加，这表明考克斯-1和考克斯-2对FSS诱导的PGE（2）释放的作用相同。胞浆磷脂酶A2（cPLA 2）是产生考克斯底物花生四烯酸的主要酶，受丝裂原活化蛋白激酶依赖性磷酸化和胞内Ca 2+浓度（[Ca 2 +]（i））调节，这两个信号传导过程均由FSS激活。抑制ERK和p38通路分别使PGE（2）释放减少53.3 +/- 8.4和32.6 +/-11.3%，而拮抗JNK通路则没有影响。此外，[Ca 2 +]（i）的螯合作用限制了FSS介导的PGE（2）浓度增加，其增加幅度为未处理剪切细胞中观察到的47.5 +/- 7.5%。剪切细胞表达更大的磷酸化cPLA 2蛋白丰度比静态细胞，然而，考克斯-2蛋白表达不受影响（P = 0.064）的FSS。在微灌注的CD中，考克斯抑制增强了血流刺激的Na重吸收，并消除了血流刺激的钾（K）分泌，但不影响慢流速下的离子转运，这意味着高小管流量激活了自分泌/旁分泌PGE（2）的释放，进而调节了血流刺激的阳离子转运。总之，FSS激活cPLA 2产生PGE（2），PGE（2）调节天然CD中流动介导的Na和K转运。我们推测膳食钠摄入调节肾小管流速，以调节CD中旁分泌PGE（2）的释放和阳离子转运。
Flores D, Liu Y, Liu W, Satlin LM, Rohatgi R. Flow-induced prostaglandin E-2 release regulates Na and K transport in the collecting duct. Am J Physiol Renal Physiol 303: F632-F638, 2012. First published June 13, 2012; doi: 10.1152/ajprenal.00169.2012.-Fluid shear stress (FSS) is a critical regulator of cation transport in the collecting duct (CD). High-dietary sodium (Na) consumption increases urine flow, Na excretion, and prostaglandin E-2 (PGE(2)) excretion. We hypothesize that increases in FSS elicited by increasing tubular flow rate induce the release of PGE(2) from renal epithelial cells into the extracellular compartment and regulate ion transport. Media retrieved from CD cells exposed to physiologic levels of FSS reveal several fold higher concentration of PGE(2) compared with static controls. Treatment of CD cells with either cyclooxygenase-1 (COX-1) or COX-2 inhibitors during exposure to FSS limited the increase in PGE(2) concentration to an equal extent, suggesting COX-1 and COX-2 contribute equally to FSS-induced PGE(2) release. Cytosolic phospholipase A2 (cPLA2), the principal enzyme that generates the COX substrate arachidonic acid, is regulated by mitogen-activated protein-kinase-dependent phosphorylation and intracellular Ca2+ concentration ([Ca2+](i)), both signaling processes, of which, are activated by FSS. Inhibition of the ERK and p38 pathways reduced PGE(2) release by 53.3 +/- 8.4 and 32.6 +/- 11.3%, respectively, while antagonizing the JNK pathway had no effect. In addition, chelation of [Ca2+](i) limited the FSS-mediated increase in PGE(2) concentration by 47.5 +/- 7.5% of that observed in untreated sheared cells. Sheared cells expressed greater phospho-cPLA2 protein abundance than static cells; however, COX-2 protein expression was unaffected (P = 0.064) by FSS. In microperfused CDs, COX inhibition enhanced flow-stimulated Na reabsorption and abolished flow-stimulated potassium (K) secretion, but did not affect ion transport at a slow flow rate, implicating that high tubular flow activates autocrine/paracrine PGE(2) release and, in turn, regulates flow-stimulated cation transport. In conclusion, FSS activates cPLA2 to generate PGE(2) that regulates flow-mediated Na and K transport in the native CD. We speculate that dietary sodium intake modulates tubular flow rate to regulate paracrine PGE(2) release and cation transport in the CD.