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Summary of our research
As diabetes progresses, the glomeruli responsible for the kidney's filtration function are destroyed, leading to proteinuria and nephrotic syndrome. Based on the world's first type 2 diabetes model zebrafish, which we announced in 2017, we have developed a diabetic nephropathy model, the zMIR/VDBP zebrafish.
In the zMIR/VDBP fish, as diabetes progresses, damage occurs in the kidney glomeruli, leading to the onset of proteinuria. By expressing the fluorescent protein EGFP in proteinuria, we have made it possible to measure the amount of proteinuria in the rearing environment (breeding tank). Pathological histological examinations of the kidney showed features similar to those of patients, such as thickening of the glomerular basement membrane, loss of foot processes, and glomerulosclerosis. RNA-seq analysis of the kidney revealed that this zebrafish exhibited gene expression patterns similar to those observed in patients. Notably, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, which is observed in the early stages, was activated, and the hypoglycemic drug metformin improved hyperglycemia and proteinuria in this zebrafish by regulating Akt phosphorylation.
The results of this study suggest that the zMIR/VDBP zebrafish will be a powerful tool for elucidating the mechanisms of onset and progression of diabetic nephropathy in humans and for developing treatments.
This work was published online in the Disease Models & Mechanisms on May 29th, 2024.
Researcher information
Yasuhito Shimada
Assistant Professor, Graduate School of Medicine, Mie University
Representative, Mie University Zebrafish Research Center
Specialized area：
Pharmacology, Disease Model Animals
Current research field：
・ Development of Human Disease Models using Zebrafish
・ Exploration of Treatments for Diabetes and Its related Diseases
Liqing Zang
Specially Appointed Associate Professor, Graduate School of Regional Innovation Studies, Mie University
Mie University Zebrafish Research Center
Specialized area：
Pharmacology, Disease Model Animals
Current research field：
・ Exploration of Therapeutic Target Genes using a Diabetic Nephropathy Model Zebrafish
・ Research on Functional Evaluation of Natural Products using Human Disease Model Zebrafish