Nasrallah Rania, Landry Anne, Scholey James W, Hébert Richard L
Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Room 1337, Ottawa, ON, Canada K1H 8M5.
Prostaglandins Leukot Essent Fatty Acids. 2004 May;70(5):455-64. doi: 10.1016/j.plefa.2003.09.004.
Mesangial cells play an important role in glomerular function. They are an important source of cyclooxygenase (COX)-derived arachidonic acid metabolites, including prostaglandin E(2) and prostacyclin. Prostacyclin receptor (IP) mRNA was amplified from cultured mesangial cell total RNA by RT-PCR. While the prostaglandin E(2) receptor subtype EP(2) was not detected, EP(1,3,4) mRNA was amplified. Also, IP protein was noted in mesangial cells, proximal tubules, inner medullary collecting ducts, and the inner and outer medulla. But no protein was detected in whole cortex preparations. Prostacyclin analogues: cicaprost and iloprost, increased cAMP levels in mesangial cells. On the other hand, arginine-vasopressin and angiotensin II increased intracellular calcium in mesangial cells, but cicaprost, iloprost and prostaglandin E(2) had no effect. Moreover, a 50% inhibition of cicaprost- and iloprost-cAMP stimulation was observed upon mesangial cell exposure to 25 and 35 mM glucose for 5 days. But no change in IP mRNA was observed at any glucose concentration or time exposure. Although 25 mM glucose had no effect on COX-1 protein levels, COX-2 was increased up to 50%. In contrast, PGIS levels were reduced by 50%. Thus, we conclude that the prostacyclin/IP system is present in cultured rat mesangial cells, coupling to a cAMP stimulatory pathway. High glucose altered both enzymes in the PGI(2) synthesis pathway, increasing COX-2 but reducing PGIS. In addition, glucose diminished the cAMP response to prostacyclin analogues. Therefore, glucose attenuates the PGI(2)/IP system in cultured rat mesangial cells.
系膜细胞在肾小球功能中发挥着重要作用。它们是环氧化酶（COX）衍生的花生四烯酸代谢产物的重要来源，包括前列腺素E（2）和前列环素。通过逆转录聚合酶链反应（RT-PCR）从培养的系膜细胞总RNA中扩增出前列环素受体（IP）mRNA。虽然未检测到前列腺素E（2）受体亚型EP（2），但扩增出了EP（1,3,4）mRNA。此外，在系膜细胞、近端小管、髓质内集合管以及内髓和外髓中均检测到IP蛋白。但在整个皮质制剂中未检测到蛋白。前列环素类似物：西卡前列素和伊洛前列素，可增加系膜细胞中的环磷酸腺苷（cAMP）水平。另一方面，精氨酸加压素和血管紧张素II可增加系膜细胞内的钙含量，但西卡前列素、伊洛前列素和前列腺素E（2）无此作用。此外，系膜细胞在25和35 mM葡萄糖中培养5天后，观察到西卡前列素和伊洛前列素刺激cAMP的作用受到50%的抑制。但在任何葡萄糖浓度或暴露时间下，IP mRNA均未观察到变化。虽然25 mM葡萄糖对COX-1蛋白水平无影响，但COX-2增加了50%。相比之下，前列环素合成酶（PGIS）水平降低了50%。因此，我们得出结论，前列环素/IP系统存在于培养的大鼠系膜细胞中，并与cAMP刺激途径偶联。高糖改变了前列环素（PGI（2））合成途径中的两种酶，增加了COX-2但降低了PGIS。此外，葡萄糖减弱了对前列环素类似物的cAMP反应。因此，葡萄糖减弱了培养的大鼠系膜细胞中的PGI（2）/IP系统。
