文章基本信息

标题：Characterization of purinergic receptor 2 signaling in podocytes from diabetic kidneys
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作者：Oleg Palygin ; Christine A. Klemens ; Elena Isaeva 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：6
页码：1-17
DOI：10.1016/j.isci.2021.102528
语种：English
出版社：Elsevier
摘要：SummaryGrowing evidence suggests that renal purinergic signaling undergoes significant remodeling during pathophysiological conditions such as diabetes. This study examined the renal P2 receptor profile and ATP-mediated calcium response from podocytes in glomeruli from kidneys with type 1 or type 2 diabetic kidney disease (DKD), using type 2 diabetic nephropathy (T2DN) rats and streptozotocin-injected Dahl salt-sensitive (type 1 diabetes) rats. A dramatic increase in the ATP-mediated intracellular calcium flux in podocytes was observed in both models. Pharmacological inhibition established that P2X4and P2X7are the major receptors contributing to the augmented ATP-mediated intracellular calcium signaling in diabetic podocytes. The transition in purinergic receptor composition from metabotropic to ionotropic may disrupt intracellular calcium homeostasis in podocytes resulting in their dysfunction and potentially further aggravating DKD progression.Graphical abstractDisplay OmittedHighlights•Diabetic podocytes have sustained intracellular Ca2+signaling in response to ATP•Podocyte purinergic receptor signaling is predominantly ionotropic in diabetes•Both type 1 and 2 diabetic podocytes have similar purinergic receptor remodeling