Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin

Kiyonari Kato, Tomoki Kosugi, Waichi Sato, Hanayo Arata-Kawai, Takenori Ozaki, Naotake Tsuboi, Isao Ito, Hideo Tawada, Yukio Yuzawa, Seiichi Matsuo, Kenji Kadomatsu, Shoichi Maruyama

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Growth factor Midkine (MK), which expresses on endothelial cells and renal proximal tubules, has been implicated in inflammation-related kidney diseases such as ischemic reperfusion-induced tubulointerstitial injury and diabetic nephropathy. The biological actions of MK are elicited through its chemotactic activity and chemokine-driven inflammatory pathway. Post-infectious glomerulonephritis is caused by the deposition of immune complexes into glomeruli by infiltrating a number of inflammatory cells. Therefore, we investigated whether MK might be involved in the pathogenesis of acute glomerulonephritis. Methods: We induced endocapillary proliferative glomerulonephritis in 129/SV mice using intraperitoneal injections of a large amount of protein. Results: In contrast to mice deficient in MK (Mdk -/-), Mdk +/+ mice induced by protein overload demonstrated more diffuse cellular proliferation in the mesangial areas and capillary lumens, eventually leading to glomerular damage and tubulointerstitial injury. This pathological observation could be attributable to neutrophil infiltration through the chemotaxis and stimulation of the MK-macrophage inflammatory protein (MIP)-2 pathway, but appeared to be due to the MK-related immunoglobulin (Ig)G deposition and C3 activation. These findings are often seen in infectious-related glomerular injury. Furthermore, the profile of MK expression was strongly consistent with that of glomerular damage and tubulointersititial injury. Conclusion: This study might provide a new insight into understanding the deleterious role of MK in endocapillary proliferative glomerulonephritis induced by protein overload.

Original languageEnglish
Pages (from-to)346-354
Number of pages9
JournalClinical and Experimental Nephrology
Volume15
Issue number3
DOIs
Publication statusPublished - 01-06-2011
Externally publishedYes

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Endotoxins
Intercellular Signaling Peptides and Proteins
Kidney
Glomerulonephritis
Wounds and Injuries
Proteins
129 Strain Mouse
Chemokine CXCL2
Proximal Kidney Tubule
Neutrophil Infiltration
Kidney Diseases
Diabetic Nephropathies
Chemotaxis
midkine
Antigen-Antibody Complex
Intraperitoneal Injections
Chemokines
Reperfusion
Endothelial Cells
Cell Count

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

Kato, Kiyonari ; Kosugi, Tomoki ; Sato, Waichi ; Arata-Kawai, Hanayo ; Ozaki, Takenori ; Tsuboi, Naotake ; Ito, Isao ; Tawada, Hideo ; Yuzawa, Yukio ; Matsuo, Seiichi ; Kadomatsu, Kenji ; Maruyama, Shoichi. / Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin. In: Clinical and Experimental Nephrology. 2011 ; Vol. 15, No. 3. pp. 346-354.
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abstract = "Background: Growth factor Midkine (MK), which expresses on endothelial cells and renal proximal tubules, has been implicated in inflammation-related kidney diseases such as ischemic reperfusion-induced tubulointerstitial injury and diabetic nephropathy. The biological actions of MK are elicited through its chemotactic activity and chemokine-driven inflammatory pathway. Post-infectious glomerulonephritis is caused by the deposition of immune complexes into glomeruli by infiltrating a number of inflammatory cells. Therefore, we investigated whether MK might be involved in the pathogenesis of acute glomerulonephritis. Methods: We induced endocapillary proliferative glomerulonephritis in 129/SV mice using intraperitoneal injections of a large amount of protein. Results: In contrast to mice deficient in MK (Mdk -/-), Mdk +/+ mice induced by protein overload demonstrated more diffuse cellular proliferation in the mesangial areas and capillary lumens, eventually leading to glomerular damage and tubulointerstitial injury. This pathological observation could be attributable to neutrophil infiltration through the chemotaxis and stimulation of the MK-macrophage inflammatory protein (MIP)-2 pathway, but appeared to be due to the MK-related immunoglobulin (Ig)G deposition and C3 activation. These findings are often seen in infectious-related glomerular injury. Furthermore, the profile of MK expression was strongly consistent with that of glomerular damage and tubulointersititial injury. Conclusion: This study might provide a new insight into understanding the deleterious role of MK in endocapillary proliferative glomerulonephritis induced by protein overload.",
author = "Kiyonari Kato and Tomoki Kosugi and Waichi Sato and Hanayo Arata-Kawai and Takenori Ozaki and Naotake Tsuboi and Isao Ito and Hideo Tawada and Yukio Yuzawa and Seiichi Matsuo and Kenji Kadomatsu and Shoichi Maruyama",
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Kato, K, Kosugi, T, Sato, W, Arata-Kawai, H, Ozaki, T, Tsuboi, N, Ito, I, Tawada, H, Yuzawa, Y, Matsuo, S, Kadomatsu, K & Maruyama, S 2011, 'Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin', Clinical and Experimental Nephrology, vol. 15, no. 3, pp. 346-354. https://doi.org/10.1007/s10157-011-0408-2

Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin. / Kato, Kiyonari; Kosugi, Tomoki; Sato, Waichi; Arata-Kawai, Hanayo; Ozaki, Takenori; Tsuboi, Naotake; Ito, Isao; Tawada, Hideo; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Maruyama, Shoichi.

In: Clinical and Experimental Nephrology, Vol. 15, No. 3, 01.06.2011, p. 346-354.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin

AU - Kato, Kiyonari

AU - Kosugi, Tomoki

AU - Sato, Waichi

AU - Arata-Kawai, Hanayo

AU - Ozaki, Takenori

AU - Tsuboi, Naotake

AU - Ito, Isao

AU - Tawada, Hideo

AU - Yuzawa, Yukio

AU - Matsuo, Seiichi

AU - Kadomatsu, Kenji

AU - Maruyama, Shoichi

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Background: Growth factor Midkine (MK), which expresses on endothelial cells and renal proximal tubules, has been implicated in inflammation-related kidney diseases such as ischemic reperfusion-induced tubulointerstitial injury and diabetic nephropathy. The biological actions of MK are elicited through its chemotactic activity and chemokine-driven inflammatory pathway. Post-infectious glomerulonephritis is caused by the deposition of immune complexes into glomeruli by infiltrating a number of inflammatory cells. Therefore, we investigated whether MK might be involved in the pathogenesis of acute glomerulonephritis. Methods: We induced endocapillary proliferative glomerulonephritis in 129/SV mice using intraperitoneal injections of a large amount of protein. Results: In contrast to mice deficient in MK (Mdk -/-), Mdk +/+ mice induced by protein overload demonstrated more diffuse cellular proliferation in the mesangial areas and capillary lumens, eventually leading to glomerular damage and tubulointerstitial injury. This pathological observation could be attributable to neutrophil infiltration through the chemotaxis and stimulation of the MK-macrophage inflammatory protein (MIP)-2 pathway, but appeared to be due to the MK-related immunoglobulin (Ig)G deposition and C3 activation. These findings are often seen in infectious-related glomerular injury. Furthermore, the profile of MK expression was strongly consistent with that of glomerular damage and tubulointersititial injury. Conclusion: This study might provide a new insight into understanding the deleterious role of MK in endocapillary proliferative glomerulonephritis induced by protein overload.

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