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Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease

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Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease. / Mulay, Shrikant R; Eberhard, Jonathan N; Desai, Jyaysi; Marschner, Julian A; Kumar, Santhosh V R; Weidenbusch, Marc; Grigorescu, Melissa; Lech, Maciej; Eltrich, Nuru; Müller, Lisa; Hans, Wolfgang; Hrabě de Angelis, Martin; Vielhauer, Volker; Hoppe, Bernd; Asplin, John; Burzlaff, Nicolai; Herrmann, Martin; Evan, Andrew; Anders, Hans-Joachim.

In: J AM SOC NEPHROL, Vol. 28, No. 3, 03.2017, p. 761-768.

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

Harvard

Mulay, SR, Eberhard, JN, Desai, J, Marschner, JA, Kumar, SVR, Weidenbusch, M, Grigorescu, M, Lech, M, Eltrich, N, Müller, L, Hans, W, Hrabě de Angelis, M, Vielhauer, V, Hoppe, B, Asplin, J, Burzlaff, N, Herrmann, M, Evan, A & Anders, H-J 2017, 'Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease', J AM SOC NEPHROL, vol. 28, no. 3, pp. 761-768. https://doi.org/10.1681/ASN.2016040486

APA

Mulay, S. R., Eberhard, J. N., Desai, J., Marschner, J. A., Kumar, S. V. R., Weidenbusch, M., Grigorescu, M., Lech, M., Eltrich, N., Müller, L., Hans, W., Hrabě de Angelis, M., Vielhauer, V., Hoppe, B., Asplin, J., Burzlaff, N., Herrmann, M., Evan, A., & Anders, H-J. (2017). Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease. J AM SOC NEPHROL, 28(3), 761-768. https://doi.org/10.1681/ASN.2016040486

Vancouver

Mulay SR, Eberhard JN, Desai J, Marschner JA, Kumar SVR, Weidenbusch M et al. Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease. J AM SOC NEPHROL. 2017 Mar;28(3):761-768. https://doi.org/10.1681/ASN.2016040486

Bibtex

@article{ce72be8cabd940b69e996114d0d21917,
title = "Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease",
abstract = "Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria.",
keywords = "Animals, Crystallization, Humans, Hyperoxaluria, Kidney Calculi, Mice, Mice, Inbred C57BL, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Journal Article",
author = "Mulay, {Shrikant R} and Eberhard, {Jonathan N} and Jyaysi Desai and Marschner, {Julian A} and Kumar, {Santhosh V R} and Marc Weidenbusch and Melissa Grigorescu and Maciej Lech and Nuru Eltrich and Lisa M{\"u}ller and Wolfgang Hans and {Hrab{\v e} de Angelis}, Martin and Volker Vielhauer and Bernd Hoppe and John Asplin and Nicolai Burzlaff and Martin Herrmann and Andrew Evan and Hans-Joachim Anders",
note = "Copyright {\textcopyright} 2017 by the American Society of Nephrology.",
year = "2017",
month = mar,
doi = "10.1681/ASN.2016040486",
language = "English",
volume = "28",
pages = "761--768",
journal = "J AM SOC NEPHROL",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "3",

}

RIS

TY - JOUR

T1 - Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease

AU - Mulay, Shrikant R

AU - Eberhard, Jonathan N

AU - Desai, Jyaysi

AU - Marschner, Julian A

AU - Kumar, Santhosh V R

AU - Weidenbusch, Marc

AU - Grigorescu, Melissa

AU - Lech, Maciej

AU - Eltrich, Nuru

AU - Müller, Lisa

AU - Hans, Wolfgang

AU - Hrabě de Angelis, Martin

AU - Vielhauer, Volker

AU - Hoppe, Bernd

AU - Asplin, John

AU - Burzlaff, Nicolai

AU - Herrmann, Martin

AU - Evan, Andrew

AU - Anders, Hans-Joachim

N1 - Copyright © 2017 by the American Society of Nephrology.

PY - 2017/3

Y1 - 2017/3

N2 - Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria.

AB - Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria.

KW - Animals

KW - Crystallization

KW - Humans

KW - Hyperoxaluria

KW - Kidney Calculi

KW - Mice

KW - Mice, Inbred C57BL

KW - Receptors, Tumor Necrosis Factor, Type I

KW - Receptors, Tumor Necrosis Factor, Type II

KW - Journal Article

U2 - 10.1681/ASN.2016040486

DO - 10.1681/ASN.2016040486

M3 - SCORING: Journal article

C2 - 27612997

VL - 28

SP - 761

EP - 768

JO - J AM SOC NEPHROL

JF - J AM SOC NEPHROL

SN - 1046-6673

IS - 3

ER -