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Updated: Jul 14, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
10:31

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy

Tomoki Kosugi1, Yukio Yuzawa, Waichi Sato

  • 1Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Laboratory Investigation; a Journal of Technical Methods and Pathology
|July 4, 2007
PubMed

Insights

Midkine (MK) is a key molecule in diabetic kidney inflammation. MK deficiency reduces tubulointerstitial damage and monocyte chemoattractant protein-1 (MCP-1) levels in diabetic nephropathy models.

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Diabetic nephropathy (DN) pathogenesis involves inflammation, though glomerular sclerosis is the primary pathology.
  • Midkine (MK), a growth factor, is investigated for its role in DN-associated inflammation.

Purpose of the Study:

  • To identify novel molecular players in inflammation during diabetic nephropathy.
  • To investigate the role of midkine (MK) in Streptozotocin-induced diabetic nephropathy.

Main Methods:

  • Utilized MK-deficient (Mdk(-/-)) and wild-type (Mdk(+/+)) mice in a Streptozotocin-induced diabetic nephropathy model.
  • Assessed tubulointerstitial damage, macrophage infiltration, and expression of MK, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1).
  • Examined MK and MCP-1 expression in high glucose-treated tubular epithelial cells and macrophages.

Main Results:

  • MK deficiency significantly reduced tubulointerstitial damage, osteopontin expression, collagen I deposition, and macrophage infiltration in diabetic mice.
  • Monocyte chemoattractant protein-1 (MCP-1) expression was lower in MK-deficient mice, while ICAM-1 was not significantly affected.
  • High glucose upregulated MK in tubular cells and enhanced MCP-1 production, an effect amplified by exogenous MK.
  • High glucose and oxidant stress increased MK expression in macrophages.
  • MK was detected in kidneys of patients with diabetic nephropathy.

Conclusions:

  • Midkine (MK) is a critical mediator of tubulointerstitial inflammation in diabetic nephropathy.
  • MK activates the monocyte chemoattractant protein-1 (MCP-1) pathway, contributing to inflammation in diabetic kidney disease.

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