Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy

Tomoki Kosugi, Yukio Yuzawa, Waichi Sato, Hanayo Arata-Kawai, Norihiko Suzuki, Noritoshi Kato, Seiichi Matsuo, Kenji Kadomatsu

Research output: Contribution to journalArticle

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Abstract

The concept that inflammation plays a crucial role in the pathogenesis of diabetic nephropathy has been recently emerging, although the principal pathology of diabetic nephropathy comprises glomerular sclerosis and associated changes in nephrons. Here, we identified the growth factor midkine (MK) as a novel key molecule involved in inflammation associated with Streptozotocin- induced diabetic nephropathy. The tubulointerstitial damage, as assessed as morphological changes, osteopontin expression, collagen I deposition and macrophage infiltration, were strikingly less in MK-deficient (Mdk -/-) mice than in Mdk+/+ mice. Monocyte chemoattractant protein (MCP)-1 expression, but not that of intercellular adhesion molecule-1, was also lower in Mdk-/- mice. High glucose upregulated MK expression in primary-cultured tubular epithelial cells, and induced MCP-1 to a larger extent in Mdk+/+ cells than in Mdk-/- cells. Correspondingly, the combination of exogenous MK and high glucose enhanced MCP-1 expression in Mdk-/- cells. Furthermore, high glucose and oxidant stress enhanced MK expression in macrophages. Consistent with the findings in the mouse model, MK expression was detected in the glomeruli, tubular epithelium and interstitium of kidneys from patients with diabetic nephropathy. Our data indicate that MK plays a critical role in the tubulointerstitial inflammation associated with diabetic nephropathy through activation of the MCP-1 pathway.

Original languageEnglish
Pages (from-to)903-913
Number of pages11
JournalLaboratory Investigation
Volume87
Issue number9
DOIs
Publication statusPublished - 01-09-2007

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Diabetic Nephropathies
Inflammation
Chemokine CCL2
Glucose
Macrophages
Osteopontin
Nephrons
Sclerosis
Intercellular Adhesion Molecule-1
Streptozocin
midkine
Oxidants
Intercellular Signaling Peptides and Proteins
Collagen
Epithelium
Epithelial Cells
Pathology
Kidney

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Kosugi, Tomoki ; Yuzawa, Yukio ; Sato, Waichi ; Arata-Kawai, Hanayo ; Suzuki, Norihiko ; Kato, Noritoshi ; Matsuo, Seiichi ; Kadomatsu, Kenji. / Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy. In: Laboratory Investigation. 2007 ; Vol. 87, No. 9. pp. 903-913.
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Kosugi, T, Yuzawa, Y, Sato, W, Arata-Kawai, H, Suzuki, N, Kato, N, Matsuo, S & Kadomatsu, K 2007, 'Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy', Laboratory Investigation, vol. 87, no. 9, pp. 903-913. https://doi.org/10.1038/labinvest.3700599

Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy. / Kosugi, Tomoki; Yuzawa, Yukio; Sato, Waichi; Arata-Kawai, Hanayo; Suzuki, Norihiko; Kato, Noritoshi; Matsuo, Seiichi; Kadomatsu, Kenji.

In: Laboratory Investigation, Vol. 87, No. 9, 01.09.2007, p. 903-913.

Research output: Contribution to journalArticle

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