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Metabolic pathways and immunometabolism in rare kidney diseases

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Metabolic pathways and immunometabolism in rare kidney diseases. / Grayson, Peter C; Eddy, Sean; Taroni, Jaclyn N; Lightfoot, Yaíma L; Mariani, Laura; Parikh, Hemang; Lindenmeyer, Maja T; Ju, Wenjun; Greene, Casey S; Godfrey, Brad; Cohen, Clemens D; Krischer, Jeffrey; Kretzler, Matthias; Merkel, Peter A; Vasculitis Clinical Research Consortium, the European Renal cDNA Bank cohort, and the Nephrotic Syndrome Study Network.

In: ANN RHEUM DIS, Vol. 77, No. 8, 08.2018, p. 1226-1233.

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

Harvard

Grayson, PC, Eddy, S, Taroni, JN, Lightfoot, YL, Mariani, L, Parikh, H, Lindenmeyer, MT, Ju, W, Greene, CS, Godfrey, B, Cohen, CD, Krischer, J, Kretzler, M, Merkel, PA & Vasculitis Clinical Research Consortium, the European Renal cDNA Bank cohort, and the Nephrotic Syndrome Study Network 2018, 'Metabolic pathways and immunometabolism in rare kidney diseases', ANN RHEUM DIS, vol. 77, no. 8, pp. 1226-1233. https://doi.org/10.1136/annrheumdis-2017-212935

APA

Grayson, P. C., Eddy, S., Taroni, J. N., Lightfoot, Y. L., Mariani, L., Parikh, H., Lindenmeyer, M. T., Ju, W., Greene, C. S., Godfrey, B., Cohen, C. D., Krischer, J., Kretzler, M., Merkel, P. A., & Vasculitis Clinical Research Consortium, the European Renal cDNA Bank cohort, and the Nephrotic Syndrome Study Network (2018). Metabolic pathways and immunometabolism in rare kidney diseases. ANN RHEUM DIS, 77(8), 1226-1233. https://doi.org/10.1136/annrheumdis-2017-212935

Vancouver

Grayson PC, Eddy S, Taroni JN, Lightfoot YL, Mariani L, Parikh H et al. Metabolic pathways and immunometabolism in rare kidney diseases. ANN RHEUM DIS. 2018 Aug;77(8):1226-1233. https://doi.org/10.1136/annrheumdis-2017-212935

Bibtex

@article{d37377065f56440abb9c1f7c602160a9,
title = "Metabolic pathways and immunometabolism in rare kidney diseases",
abstract = "OBJECTIVES: To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis.METHODS: Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated renal biopsies were obtained at time of diagnosis and microdissected into glomerular and tubulointerstitial compartments. Microarray-derived differential gene expression of 88 genes representing critical enzymes of metabolic pathways and 25 genes related to immune cell markers was compared between disease groups. Correlation analyses measured relationships between metabolic pathways, kidney function and cytokine production.RESULTS: Reduced steady state levels of mRNA species were enriched in pathways of oxidative phosphorylation and increased in the pentose phosphate pathway (PPP) with maximal perturbation in AAV and SLE followed by NS, and least in LD. Transcript regulation was isozymes specific with robust regulation in hexokinases, enolases and glucose transporters. Intercorrelation networks were observed between enzymes of the PPP (eg, transketolase) and macrophage markers (eg, CD68) (r=0.49, p<0.01). Increased PPP transcript levels were associated with reduced glomerular filtration rate in the glomerular (r=-0.49, p<0.01) and tubulointerstitial (r=-0.41, p<0.01) compartments. PPP expression and tumour necrosis factor activation were tightly co-expressed (r=0.70, p<0.01).CONCLUSION: This study demonstrated concordant alterations of the renal transcriptome consistent with metabolic reprogramming across different forms of glomerulonephritis. Activation of the PPP was tightly linked with intrarenal macrophage marker expression, reduced kidney function and increased production of cytokines. Modulation of glucose metabolism may offer novel immune-modulatory therapeutic approaches in rare kidney diseases.",
keywords = "Journal Article",
author = "Grayson, {Peter C} and Sean Eddy and Taroni, {Jaclyn N} and Lightfoot, {Ya{\'i}ma L} and Laura Mariani and Hemang Parikh and Lindenmeyer, {Maja T} and Wenjun Ju and Greene, {Casey S} and Brad Godfrey and Cohen, {Clemens D} and Jeffrey Krischer and Matthias Kretzler and Merkel, {Peter A} and {Vasculitis Clinical Research Consortium, the European Renal cDNA Bank cohort, and the Nephrotic Syndrome Study Network}",
note = "{\textcopyright} Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.",
year = "2018",
month = aug,
doi = "10.1136/annrheumdis-2017-212935",
language = "English",
volume = "77",
pages = "1226--1233",
journal = "ANN RHEUM DIS",
issn = "0003-4967",
publisher = "BMJ PUBLISHING GROUP",
number = "8",

}

RIS

TY - JOUR

T1 - Metabolic pathways and immunometabolism in rare kidney diseases

AU - Grayson, Peter C

AU - Eddy, Sean

AU - Taroni, Jaclyn N

AU - Lightfoot, Yaíma L

AU - Mariani, Laura

AU - Parikh, Hemang

AU - Lindenmeyer, Maja T

AU - Ju, Wenjun

AU - Greene, Casey S

AU - Godfrey, Brad

AU - Cohen, Clemens D

AU - Krischer, Jeffrey

AU - Kretzler, Matthias

AU - Merkel, Peter A

AU - Vasculitis Clinical Research Consortium, the European Renal cDNA Bank cohort, and the Nephrotic Syndrome Study Network

N1 - © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PY - 2018/8

Y1 - 2018/8

N2 - OBJECTIVES: To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis.METHODS: Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated renal biopsies were obtained at time of diagnosis and microdissected into glomerular and tubulointerstitial compartments. Microarray-derived differential gene expression of 88 genes representing critical enzymes of metabolic pathways and 25 genes related to immune cell markers was compared between disease groups. Correlation analyses measured relationships between metabolic pathways, kidney function and cytokine production.RESULTS: Reduced steady state levels of mRNA species were enriched in pathways of oxidative phosphorylation and increased in the pentose phosphate pathway (PPP) with maximal perturbation in AAV and SLE followed by NS, and least in LD. Transcript regulation was isozymes specific with robust regulation in hexokinases, enolases and glucose transporters. Intercorrelation networks were observed between enzymes of the PPP (eg, transketolase) and macrophage markers (eg, CD68) (r=0.49, p<0.01). Increased PPP transcript levels were associated with reduced glomerular filtration rate in the glomerular (r=-0.49, p<0.01) and tubulointerstitial (r=-0.41, p<0.01) compartments. PPP expression and tumour necrosis factor activation were tightly co-expressed (r=0.70, p<0.01).CONCLUSION: This study demonstrated concordant alterations of the renal transcriptome consistent with metabolic reprogramming across different forms of glomerulonephritis. Activation of the PPP was tightly linked with intrarenal macrophage marker expression, reduced kidney function and increased production of cytokines. Modulation of glucose metabolism may offer novel immune-modulatory therapeutic approaches in rare kidney diseases.

AB - OBJECTIVES: To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis.METHODS: Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated renal biopsies were obtained at time of diagnosis and microdissected into glomerular and tubulointerstitial compartments. Microarray-derived differential gene expression of 88 genes representing critical enzymes of metabolic pathways and 25 genes related to immune cell markers was compared between disease groups. Correlation analyses measured relationships between metabolic pathways, kidney function and cytokine production.RESULTS: Reduced steady state levels of mRNA species were enriched in pathways of oxidative phosphorylation and increased in the pentose phosphate pathway (PPP) with maximal perturbation in AAV and SLE followed by NS, and least in LD. Transcript regulation was isozymes specific with robust regulation in hexokinases, enolases and glucose transporters. Intercorrelation networks were observed between enzymes of the PPP (eg, transketolase) and macrophage markers (eg, CD68) (r=0.49, p<0.01). Increased PPP transcript levels were associated with reduced glomerular filtration rate in the glomerular (r=-0.49, p<0.01) and tubulointerstitial (r=-0.41, p<0.01) compartments. PPP expression and tumour necrosis factor activation were tightly co-expressed (r=0.70, p<0.01).CONCLUSION: This study demonstrated concordant alterations of the renal transcriptome consistent with metabolic reprogramming across different forms of glomerulonephritis. Activation of the PPP was tightly linked with intrarenal macrophage marker expression, reduced kidney function and increased production of cytokines. Modulation of glucose metabolism may offer novel immune-modulatory therapeutic approaches in rare kidney diseases.

KW - Journal Article

U2 - 10.1136/annrheumdis-2017-212935

DO - 10.1136/annrheumdis-2017-212935

M3 - SCORING: Journal article

C2 - 29724730

VL - 77

SP - 1226

EP - 1233

JO - ANN RHEUM DIS

JF - ANN RHEUM DIS

SN - 0003-4967

IS - 8

ER -