期刊
ISCIENCE
卷 24, 期 6, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.102528
关键词
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资金
- Department of Veterans' Affairs [I01 BX004024]
- National Institutes of Health [R35 HL135749, R00 DK105160, T32 HL134643, R01 DK126720]
- NIDDK Diabetic Complications Consortium [RRID:SCR_001415, DK076169, DK115255]
The study found that renal purinergic signaling undergoes significant remodeling in diabetes, leading to an increase in ATP-mediated intracellular calcium flux in podocytes. P2X4 and P2X7 were identified as the major receptors contributing to the augmented ATP-mediated intracellular calcium signaling in diabetic podocytes.
Growing 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 P2X4 and P2X7 are 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.
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