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

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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.

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

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)

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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, 15(3), 346-354. https://doi.org/10.1007/s10157-011-0408-2