Related Experiment Video
Updated: Feb 22, 2026
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Identification of a protective proteomic signature and a potential therapeutic target in diabetic nephropathy
Nicholas Chun1, Christina M Wyatt1, John C He1
1Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Abstract:
In a recent paper in Nature Medicine, Qi et al. set out to identify protective pathways in patients with longstanding diabetes who do not develop diabetic nephropathy. Unbiased proteomic analysis of kidney tissue identified a unique protein signature in unaffected individuals. Studies in vitro and in murine models identified the highly upregulated glycolytic enzyme pyruvate kinase M2 as a potential therapeutic target to prevent or treat diabetic nephropathy.
Insights
Researchers identified a unique protein signature in patients with diabetes but without kidney disease. The glycolytic enzyme pyruvate kinase M2 may be a therapeutic target for preventing or treating diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Diabetic nephropathy is a common complication of longstanding diabetes.
- Identifying protective mechanisms in patients resistant to nephropathy is crucial for therapeutic development.
Purpose of the Study:
- To identify protective molecular pathways in patients with diabetes who do not develop diabetic nephropathy.
- To investigate potential therapeutic targets for preventing or treating diabetic nephropathy.
Main Methods:
- Unbiased proteomic analysis of kidney tissue from patients with and without diabetic nephropathy.
- In vitro studies using cell cultures.
- Murine models of diabetic nephropathy.
Main Results:
- A unique protein signature was identified in the kidneys of individuals resistant to diabetic nephropathy.
- The glycolytic enzyme pyruvate kinase M2 (PKM2) was found to be highly upregulated in these individuals.
- PKM2 was identified as a potential therapeutic target.
Conclusions:
- Pyruvate kinase M2 plays a significant role in the protective pathways against diabetic nephropathy.
- Targeting PKM2 may offer a novel therapeutic strategy for managing diabetic kidney disease.
