Characterization of purinergic receptor 2 signaling in podocytes from diabetic kidneys

Oleg Palygin; Christine A. Klemens; Elena Isaeva; Vladislav Levchenko; Denisha R. Spires; Lashodya V. Dissanayake; Oksana Nikolaienko; Daria V. Ilatovskaya; Alexander Staruschenko

doi:10.1016/j.isci.2021.102528

Characterization of purinergic receptor 2 signaling in podocytes from diabetic kidneys

Oleg Palygin
, Christine A. Klemens
, Elena Isaeva
, Vladislav Levchenko
, Denisha R. Spires
, Lashodya V. Dissanayake
, Oksana Nikolaienko
, Daria V. Ilatovskaya
, Alexander Staruschenko

Kidney Disease Research Center

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

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.

Original language	English (US)
Article number	102528
Journal	iScience
Volume	24
Issue number	6
DOIs	https://doi.org/10.1016/j.isci.2021.102528
State	Published - Jun 25 2021

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SDG 3 Good Health and Well-being

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title = "Characterization of purinergic receptor 2 signaling in podocytes from diabetic kidneys",

abstract = "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.",

author = "Oleg Palygin and Klemens, \{Christine A.\} and Elena Isaeva and Vladislav Levchenko and Spires, \{Denisha R.\} and Dissanayake, \{Lashodya V.\} and Oksana Nikolaienko and Ilatovskaya, \{Daria V.\} and Alexander Staruschenko",

note = "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: {\textcopyright} 2021",

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doi = "10.1016/j.isci.2021.102528",

language = "English (US)",

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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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Characterization of purinergic receptor 2 signaling in podocytes from diabetic kidneys

Abstract

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