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P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis

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P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis. / Rennert, Laura; Zschiedrich, Stefan; Sandner, Lukas; Hartleben, Björn; Cicko, Sanja; Ayata, Cemil Korcan; Meyer, Charlotte; Zech, Andreas; Zeiser, Robert; Huber, Tobias B; Idzko, Marco; Grahammer, Florian.

In: FRONT IMMUNOL, Vol. 9, 2018, p. 1589.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rennert, L, Zschiedrich, S, Sandner, L, Hartleben, B, Cicko, S, Ayata, CK, Meyer, C, Zech, A, Zeiser, R, Huber, TB, Idzko, M & Grahammer, F 2018, 'P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis', FRONT IMMUNOL, vol. 9, pp. 1589. https://doi.org/10.3389/fimmu.2018.01589

APA

Rennert, L., Zschiedrich, S., Sandner, L., Hartleben, B., Cicko, S., Ayata, C. K., Meyer, C., Zech, A., Zeiser, R., Huber, T. B., Idzko, M., & Grahammer, F. (2018). P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis. FRONT IMMUNOL, 9, 1589. https://doi.org/10.3389/fimmu.2018.01589

Vancouver

Rennert L, Zschiedrich S, Sandner L, Hartleben B, Cicko S, Ayata CK et al. P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis. FRONT IMMUNOL. 2018;9:1589. https://doi.org/10.3389/fimmu.2018.01589

Bibtex

@article{4b67012bf687492fb6eccfe375c0ef52,
title = "P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis",
abstract = "Endogenously released adenosine-5'-triphosphate (ATP) is a key regulator of physiological function and inflammatory responses in the kidney. Genetic or pharmacological inhibition of purinergic receptors has been linked to attenuation of inflammatory disorders and hence constitutes promising new avenues for halting and reverting inflammatory renal diseases. However, the involvement of purinergic receptors in glomerulonephritis (GN) has only been incompletely mapped. Here, we demonstrate that induction of GN in an experimental antibody-mediated GN model results in a significant increase of urinary ATP-levels and an upregulation of P2Y2R expression in resident kidney cells as well as infiltrating leukocytes pointing toward a possible role of the ATP/P2Y2R-axis in glomerular disease initiation. In agreement, decreasing extracellular ATP-levels or inhibition of P2R during induction of antibody-mediated GN leads to a reduction in all cardinal features of GN such as proteinuria, glomerulosclerosis, and renal failure. The specific involvement of P2Y2R could be further substantiated by demonstrating the protective effect of the lack of P2Y2R in antibody-mediated GN. To systematically differentiate between the function of P2Y2R on resident renal cells versus infiltrating leukocytes, we performed bone marrow-chimera experiments revealing that P2Y2R on hematopoietic cells is the main driver of the ATP/P2Y2R-mediated disease progression in antibody-mediated GN. Thus, these data unravel an important pro-inflammatory role for P2Y2R in the pathogenesis of GN.",
keywords = "Journal Article",
author = "Laura Rennert and Stefan Zschiedrich and Lukas Sandner and Bj{\"o}rn Hartleben and Sanja Cicko and Ayata, {Cemil Korcan} and Charlotte Meyer and Andreas Zech and Robert Zeiser and Huber, {Tobias B} and Marco Idzko and Florian Grahammer",
year = "2018",
doi = "10.3389/fimmu.2018.01589",
language = "English",
volume = "9",
pages = "1589",
journal = "FRONT IMMUNOL",
issn = "1664-3224",
publisher = "Lausanne : Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis

AU - Rennert, Laura

AU - Zschiedrich, Stefan

AU - Sandner, Lukas

AU - Hartleben, Björn

AU - Cicko, Sanja

AU - Ayata, Cemil Korcan

AU - Meyer, Charlotte

AU - Zech, Andreas

AU - Zeiser, Robert

AU - Huber, Tobias B

AU - Idzko, Marco

AU - Grahammer, Florian

PY - 2018

Y1 - 2018

N2 - Endogenously released adenosine-5'-triphosphate (ATP) is a key regulator of physiological function and inflammatory responses in the kidney. Genetic or pharmacological inhibition of purinergic receptors has been linked to attenuation of inflammatory disorders and hence constitutes promising new avenues for halting and reverting inflammatory renal diseases. However, the involvement of purinergic receptors in glomerulonephritis (GN) has only been incompletely mapped. Here, we demonstrate that induction of GN in an experimental antibody-mediated GN model results in a significant increase of urinary ATP-levels and an upregulation of P2Y2R expression in resident kidney cells as well as infiltrating leukocytes pointing toward a possible role of the ATP/P2Y2R-axis in glomerular disease initiation. In agreement, decreasing extracellular ATP-levels or inhibition of P2R during induction of antibody-mediated GN leads to a reduction in all cardinal features of GN such as proteinuria, glomerulosclerosis, and renal failure. The specific involvement of P2Y2R could be further substantiated by demonstrating the protective effect of the lack of P2Y2R in antibody-mediated GN. To systematically differentiate between the function of P2Y2R on resident renal cells versus infiltrating leukocytes, we performed bone marrow-chimera experiments revealing that P2Y2R on hematopoietic cells is the main driver of the ATP/P2Y2R-mediated disease progression in antibody-mediated GN. Thus, these data unravel an important pro-inflammatory role for P2Y2R in the pathogenesis of GN.

AB - Endogenously released adenosine-5'-triphosphate (ATP) is a key regulator of physiological function and inflammatory responses in the kidney. Genetic or pharmacological inhibition of purinergic receptors has been linked to attenuation of inflammatory disorders and hence constitutes promising new avenues for halting and reverting inflammatory renal diseases. However, the involvement of purinergic receptors in glomerulonephritis (GN) has only been incompletely mapped. Here, we demonstrate that induction of GN in an experimental antibody-mediated GN model results in a significant increase of urinary ATP-levels and an upregulation of P2Y2R expression in resident kidney cells as well as infiltrating leukocytes pointing toward a possible role of the ATP/P2Y2R-axis in glomerular disease initiation. In agreement, decreasing extracellular ATP-levels or inhibition of P2R during induction of antibody-mediated GN leads to a reduction in all cardinal features of GN such as proteinuria, glomerulosclerosis, and renal failure. The specific involvement of P2Y2R could be further substantiated by demonstrating the protective effect of the lack of P2Y2R in antibody-mediated GN. To systematically differentiate between the function of P2Y2R on resident renal cells versus infiltrating leukocytes, we performed bone marrow-chimera experiments revealing that P2Y2R on hematopoietic cells is the main driver of the ATP/P2Y2R-mediated disease progression in antibody-mediated GN. Thus, these data unravel an important pro-inflammatory role for P2Y2R in the pathogenesis of GN.

KW - Journal Article

U2 - 10.3389/fimmu.2018.01589

DO - 10.3389/fimmu.2018.01589

M3 - SCORING: Journal article

C2 - 30061884

VL - 9

SP - 1589

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -