The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease

Atsushi Hashikata, Akiko Yamashita, Shigeki Suzuki, Shintaro Nagayasu, Takanori Shinjo, Ataru Taniguchi, Mitsuo Fukushima, Yoshikatsu Nakai, Kazuko Nin, Naoya Watanabe, Tomoichiro Asano, Yoshimitsu Abiko, Akifumi Kushiyama, Shoichiro Nagasaka, Fusanori Nishimura

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BackgroundChronic kidney disease (CKD) is an important risk factor for coronary heart disease, and previous studies indicated the involvement of low-grade inflammation in the pathogenesis of CKD.MethodsThe study was designed to (i) identify and confirm genes and their products upregulated in mesangial cells cocultured with endotoxin-stimulated macrophages and (ii) determine the clinical relevance of genes and proteins upregulated in mesangial cells under inflammatory conditions by an epidemiological approach.ResultsDNA microarray analysis revealed upregulated expression of many genes and their products including several cytokines and chemokines, as well as the inflammatory marker, lipocalin 2 gene. The gene expression and protein upregulation of lipocalin 2 were synergistically affected by endotoxin and tumor necrosis factor (TNF)-α stimulation. In human studies, lipocalin 2 level was significantly associated with creatinine (r = 0.419, P < 0.001) and negatively associated with eGFR (r = -0.365, P < 0.001). Multiple logistic regression analysis revealed a significant association between lipocalin 2 and soluble tumor necrosis factor receptor 2 (sTNF-R2), eGFR and uric acid in general subjects attending regular annual medical check-up (n = 420). When subjects with diabetes were excluded from the analysis, lipocalin 2 remained associated with sTNF-R2, eGFR and uric acid.ConclusionsSince an activated TNF system, as demonstrated by elevated sTNF-R2, and elevated uric acid were recently implicated in an elevated CKD risk, we conclude that inflammation could play an important role in the pathogenesis of CKD, and that lipocalin 2 is a potential universal marker for impaired kidney function. Furthermore, the results obtained by the current microarray analysis could improve the understanding of gene profiles associated with the pathophysiology of CKD under inflammatory conditions.

Original languageEnglish
Pages (from-to)611-618
Number of pages8
JournalNephrology Dialysis Transplantation
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Chronic Renal Insufficiency
Receptors, Tumor Necrosis Factor, Type II
Inflammation
Uric Acid
Mesangial Cells
Microarray Analysis
Endotoxins
Tumor Necrosis Factor-alpha
Genes
Gene Expression
Kidney Diseases
Chemokines
Coronary Disease
Lipocalin-2
Creatinine
Proteins
Up-Regulation
Logistic Models
Macrophages
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

Cite this

The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease. / Hashikata, Atsushi; Yamashita, Akiko; Suzuki, Shigeki; Nagayasu, Shintaro; Shinjo, Takanori; Taniguchi, Ataru; Fukushima, Mitsuo; Nakai, Yoshikatsu; Nin, Kazuko; Watanabe, Naoya; Asano, Tomoichiro; Abiko, Yoshimitsu; Kushiyama, Akifumi; Nagasaka, Shoichiro; Nishimura, Fusanori.

In: Nephrology Dialysis Transplantation, Vol. 29, No. 3, 03.2014, p. 611-618.

Research output: Contribution to journalArticle

Hashikata, A, Yamashita, A, Suzuki, S, Nagayasu, S, Shinjo, T, Taniguchi, A, Fukushima, M, Nakai, Y, Nin, K, Watanabe, N, Asano, T, Abiko, Y, Kushiyama, A, Nagasaka, S & Nishimura, F 2014, 'The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease', Nephrology Dialysis Transplantation, vol. 29, no. 3, pp. 611-618. https://doi.org/10.1093/ndt/gft449
Hashikata, Atsushi ; Yamashita, Akiko ; Suzuki, Shigeki ; Nagayasu, Shintaro ; Shinjo, Takanori ; Taniguchi, Ataru ; Fukushima, Mitsuo ; Nakai, Yoshikatsu ; Nin, Kazuko ; Watanabe, Naoya ; Asano, Tomoichiro ; Abiko, Yoshimitsu ; Kushiyama, Akifumi ; Nagasaka, Shoichiro ; Nishimura, Fusanori. / The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease. In: Nephrology Dialysis Transplantation. 2014 ; Vol. 29, No. 3. pp. 611-618.
@article{3c133ff4a0db47d4a24cdacb2a67defb,
title = "The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease",
abstract = "BackgroundChronic kidney disease (CKD) is an important risk factor for coronary heart disease, and previous studies indicated the involvement of low-grade inflammation in the pathogenesis of CKD.MethodsThe study was designed to (i) identify and confirm genes and their products upregulated in mesangial cells cocultured with endotoxin-stimulated macrophages and (ii) determine the clinical relevance of genes and proteins upregulated in mesangial cells under inflammatory conditions by an epidemiological approach.ResultsDNA microarray analysis revealed upregulated expression of many genes and their products including several cytokines and chemokines, as well as the inflammatory marker, lipocalin 2 gene. The gene expression and protein upregulation of lipocalin 2 were synergistically affected by endotoxin and tumor necrosis factor (TNF)-α stimulation. In human studies, lipocalin 2 level was significantly associated with creatinine (r = 0.419, P < 0.001) and negatively associated with eGFR (r = -0.365, P < 0.001). Multiple logistic regression analysis revealed a significant association between lipocalin 2 and soluble tumor necrosis factor receptor 2 (sTNF-R2), eGFR and uric acid in general subjects attending regular annual medical check-up (n = 420). When subjects with diabetes were excluded from the analysis, lipocalin 2 remained associated with sTNF-R2, eGFR and uric acid.ConclusionsSince an activated TNF system, as demonstrated by elevated sTNF-R2, and elevated uric acid were recently implicated in an elevated CKD risk, we conclude that inflammation could play an important role in the pathogenesis of CKD, and that lipocalin 2 is a potential universal marker for impaired kidney function. Furthermore, the results obtained by the current microarray analysis could improve the understanding of gene profiles associated with the pathophysiology of CKD under inflammatory conditions.",
author = "Atsushi Hashikata and Akiko Yamashita and Shigeki Suzuki and Shintaro Nagayasu and Takanori Shinjo and Ataru Taniguchi and Mitsuo Fukushima and Yoshikatsu Nakai and Kazuko Nin and Naoya Watanabe and Tomoichiro Asano and Yoshimitsu Abiko and Akifumi Kushiyama and Shoichiro Nagasaka and Fusanori Nishimura",
year = "2014",
month = "3",
doi = "10.1093/ndt/gft449",
language = "English",
volume = "29",
pages = "611--618",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease

AU - Hashikata, Atsushi

AU - Yamashita, Akiko

AU - Suzuki, Shigeki

AU - Nagayasu, Shintaro

AU - Shinjo, Takanori

AU - Taniguchi, Ataru

AU - Fukushima, Mitsuo

AU - Nakai, Yoshikatsu

AU - Nin, Kazuko

AU - Watanabe, Naoya

AU - Asano, Tomoichiro

AU - Abiko, Yoshimitsu

AU - Kushiyama, Akifumi

AU - Nagasaka, Shoichiro

AU - Nishimura, Fusanori

PY - 2014/3

Y1 - 2014/3

N2 - BackgroundChronic kidney disease (CKD) is an important risk factor for coronary heart disease, and previous studies indicated the involvement of low-grade inflammation in the pathogenesis of CKD.MethodsThe study was designed to (i) identify and confirm genes and their products upregulated in mesangial cells cocultured with endotoxin-stimulated macrophages and (ii) determine the clinical relevance of genes and proteins upregulated in mesangial cells under inflammatory conditions by an epidemiological approach.ResultsDNA microarray analysis revealed upregulated expression of many genes and their products including several cytokines and chemokines, as well as the inflammatory marker, lipocalin 2 gene. The gene expression and protein upregulation of lipocalin 2 were synergistically affected by endotoxin and tumor necrosis factor (TNF)-α stimulation. In human studies, lipocalin 2 level was significantly associated with creatinine (r = 0.419, P < 0.001) and negatively associated with eGFR (r = -0.365, P < 0.001). Multiple logistic regression analysis revealed a significant association between lipocalin 2 and soluble tumor necrosis factor receptor 2 (sTNF-R2), eGFR and uric acid in general subjects attending regular annual medical check-up (n = 420). When subjects with diabetes were excluded from the analysis, lipocalin 2 remained associated with sTNF-R2, eGFR and uric acid.ConclusionsSince an activated TNF system, as demonstrated by elevated sTNF-R2, and elevated uric acid were recently implicated in an elevated CKD risk, we conclude that inflammation could play an important role in the pathogenesis of CKD, and that lipocalin 2 is a potential universal marker for impaired kidney function. Furthermore, the results obtained by the current microarray analysis could improve the understanding of gene profiles associated with the pathophysiology of CKD under inflammatory conditions.

AB - BackgroundChronic kidney disease (CKD) is an important risk factor for coronary heart disease, and previous studies indicated the involvement of low-grade inflammation in the pathogenesis of CKD.MethodsThe study was designed to (i) identify and confirm genes and their products upregulated in mesangial cells cocultured with endotoxin-stimulated macrophages and (ii) determine the clinical relevance of genes and proteins upregulated in mesangial cells under inflammatory conditions by an epidemiological approach.ResultsDNA microarray analysis revealed upregulated expression of many genes and their products including several cytokines and chemokines, as well as the inflammatory marker, lipocalin 2 gene. The gene expression and protein upregulation of lipocalin 2 were synergistically affected by endotoxin and tumor necrosis factor (TNF)-α stimulation. In human studies, lipocalin 2 level was significantly associated with creatinine (r = 0.419, P < 0.001) and negatively associated with eGFR (r = -0.365, P < 0.001). Multiple logistic regression analysis revealed a significant association between lipocalin 2 and soluble tumor necrosis factor receptor 2 (sTNF-R2), eGFR and uric acid in general subjects attending regular annual medical check-up (n = 420). When subjects with diabetes were excluded from the analysis, lipocalin 2 remained associated with sTNF-R2, eGFR and uric acid.ConclusionsSince an activated TNF system, as demonstrated by elevated sTNF-R2, and elevated uric acid were recently implicated in an elevated CKD risk, we conclude that inflammation could play an important role in the pathogenesis of CKD, and that lipocalin 2 is a potential universal marker for impaired kidney function. Furthermore, the results obtained by the current microarray analysis could improve the understanding of gene profiles associated with the pathophysiology of CKD under inflammatory conditions.

UR - http://www.scopus.com/inward/record.url?scp=84895730519&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895730519&partnerID=8YFLogxK

U2 - 10.1093/ndt/gft449

DO - 10.1093/ndt/gft449

M3 - Article

C2 - 24235082

AN - SCOPUS:84895730519

VL - 29

SP - 611

EP - 618

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 3

ER -