Thromboxane A2/ prostaglandin H2 receptors in streptozotocin-induced diabetes: Effects of insulin therapy in the rat

Downregulation of Thromboxane A2 Receptor Occurs Mainly via Nuclear Factor-KappaB Signaling Pathway in Rat Renal Artery

“…On the other hand, downregulation of TP receptors occurs in pregnancy and diabetes [8–10]. In the present study, organ culture per se induced downregulation of TP receptors in rat renal smooth muscle cells.…”

“…In the present study, organ culture per se induced downregulation of TP receptors in rat renal smooth muscle cells. This simulates TP receptor downregulation which is a phenomenon seen in pregnancy and diabetes [8–10]. Thus, organ culture method may be a useful model for studying the underlying molecular mechanisms responsible for regulation of the TP receptor expression.…”

“…The phenomenon of decreased contractile response of vascular smooth muscle cells to TP receptor agonist U46619 was also seen in streptozotocin-induced diabetic rats [10]. Interestingly, renal production of TXA 2 increased in diabetes [11], while TP receptor affinity and the receptor-mediated vasoconstriction decreased [9, 10]. Thus, the downregulation of TP receptors in renal vascular smooth muscle cells most likely serves as a protective mechanism to prevent renal ischemia.…”

Transcriptional Down-Regulation of Thromboxane A₂ Receptor Expression via Activation of MAPK ERK1/2, p38/NF-κB Pathways

“…Enhanced thromboxane synthesis has been linked to cardiovascular diseases including acute myocardial ischemia [58], heart failure [59] and diabetes [60] in clinic. In contrast, the depressed TP receptor-mediated responsiveness in the aortic segments has been observed in streptozotocin-induced diabetic rats, while insulin therapy reversed the decreased contractile responses [13]. The down-regulation of TP receptors and suppressed contractile responses of vascular segments have been seen in various types of arteries during organ culture and our study showed that the activation of MAPK/NF-ĸB pathways is highly associated with this down-regulation.…”

“…Growth factors such as platelet-derived growth factor and basic fibroblast growth factor can modify TP receptor expression [12]. Interestingly, studies have shown that in streptozotocin-induced diabetic rats there is a decreased responsiveness of aortic segments to the selective TP receptor agonist U46619, which can be reversed by insulin therapy [13], indicating a down-regulation of TP receptors. In placentas from diabetic pregnancies, TP receptor affinity and vasoconstrictor responses to U46619 are reduced [14].…”