TY - JOUR
T1 - Characterization of purinergic receptor 2 signaling in podocytes from diabetic kidneys
AU - Palygin, Oleg
AU - Klemens, Christine A.
AU - Isaeva, Elena
AU - Levchenko, Vladislav
AU - Spires, Denisha R.
AU - Dissanayake, Lashodya V.
AU - Nikolaienko, Oksana
AU - Ilatovskaya, Daria V.
AU - Staruschenko, Alexander
N1 - Funding Information:
This work was supported by Department of Veterans' Affairs , Grant I01 BX004024 (to AS), National Institutes of Health Grants R35 HL135749 (to AS), R00 DK10516 0 to (DVI), and T32 HL134643 (CVC A.O. Smith Fellowship to CAK), R01 DK126720 (to OP), and NIDDK Diabetic Complications Consortium ( RRID:SCR_001415 , www.diacomp.org ), grants DK076169 and DK115255 (to AS).
Publisher Copyright:
© 2021
PY - 2021/6/25
Y1 - 2021/6/25
N2 - 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.
AB - 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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U2 - 10.1016/j.isci.2021.102528
DO - 10.1016/j.isci.2021.102528
M3 - Article
AN - SCOPUS:85106559673
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 6
M1 - 102528
ER -
