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Updated: Jun 2, 2025
10:37
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
94
IGFBP2 and IGFBP4 interact to activate complement pathway in diabetic kidney disease
Jieling Liang1,2, Yangxiao Huang2, Daping Peng2
1Guangdong Medical University, Dongguan, China.
Renal Failure
|January 14, 2025
Summary
Insulin-like growth factor-binding proteins 2 (IGFBP2) and 4 (IGFBP4) activate the complement pathway in macrophages, leading to podocyte apoptosis and diabetic kidney disease (DKD) progression.
Area of Science:
- Nephrology
- Immunology
- Endocrinology
Background:
- Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease worldwide.
- Insulin-like growth factor-binding proteins 2 (IGFBP2) and 4 (IGFBP4) are emerging as potential DKD biomarkers.
- The role of complement pathway overactivation in DKD pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the roles of IGFBP2, IGFBP4, and complement activation in DKD.
- To elucidate the molecular mechanisms linking these factors to DKD development.
Main Methods:
- Proteomic analysis of blood samples from DKD patients.
- In vitro studies using HK-2 and THP-1 cell lines.
- In vivo experiments in DKD mouse models.
- Investigation of primary human renal podocyte responses.
Main Results:
- Elevated IGFBP2 and IGFBP4 levels were found in DKD patients and mice.
- DKD mice showed increased IGFBP2/IGFBP4, complement activation, and worsened renal function.
- High glucose and DKD serum increased IGFBP2/IGFBP4 in HK-2 cells, promoting M1 macrophage polarization and complement activation.
- Macrophage-derived factors, not IGFBP2/IGFBP4 alone, impaired podocyte growth.
Conclusions:
- IGFBP2 and IGFBP4 interact to activate the complement pathway in macrophages.
- This macrophage-mediated complement activation induces podocyte apoptosis.
- The IGFBP2/IGFBP4-macrophage-complement axis is a key driver in diabetic kidney disease progression.
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