PUBLICATION
Development of a novel zebrafish model of diabetic nephropathy
- Authors
- Zang, L., Saitoh, S., Katayama, K., Zhou, W., Nishimura, N., Shimada, Y.
- ID
- ZDB-PUB-240516-3
- Date
- 2024
- Source
- Disease models & mechanisms 17(5): (Journal)
- Registered Authors
- Shimada, Yasuhito, Zhou, Weibin
- Keywords
- Diabetic nephropathy, Glomerular hypertrophy, Obesity, Proteinuria, Type 2 diabetes, Zebrafish
- MeSH Terms
-
- Disease Models, Animal*
- Diabetic Nephropathies*/metabolism
- Diabetic Nephropathies*/pathology
- Animals, Genetically Modified
- Kidney Glomerulus/drug effects
- Kidney Glomerulus/metabolism
- Kidney Glomerulus/pathology
- Phosphatidylinositol 3-Kinases/metabolism
- Hyperglycemia*/complications
- Hyperglycemia*/pathology
- Kidney/drug effects
- Kidney/metabolism
- Kidney/pathology
- Zebrafish*
- Animals
- Humans
- Metformin/pharmacology
- Metformin/therapeutic use
- Phosphorylation/drug effects
- Proto-Oncogene Proteins c-akt*/metabolism
- Proteinuria*
- Enzyme Activation/drug effects
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Signal Transduction*/drug effects
- PubMed
- 38747698 Full text @ Dis. Model. Mech.
Citation
Zang, L., Saitoh, S., Katayama, K., Zhou, W., Nishimura, N., Shimada, Y. (2024) Development of a novel zebrafish model of diabetic nephropathy. Disease models & mechanisms. 17(5):.
Abstract
Diabetic nephropathy (DN) is a substantial healthcare challenge as a complication of diabetes, owing to the high risk of morbidity and mortality involved. Although significant progress has been made in understanding the pathogenesis of DN, more efficient models are required to develop new therapeutics. Here, we created a DN model in zebrafish by crossing diabetic Tg(acta1:dnIGF1R-EGFP) and proteinuria-tracing Tg(l-fabp::VDBP-GFP) lines, named zMIR/VDBP. Overfed adult zMIR/VDBP fish developed severe hyperglycemia and proteinuria, which were not observed in wild-type zebrafish. Renal histopathology revealed human DN-like characteristics, such as glomerular basement membrane thickening, foot process effacement, and glomerular sclerosis. Glomerular dysfunction is restored upon calorie restriction. RNA sequencing (RNA-seq) analysis demonstrated that zebrafish DN kidneys exhibited transcriptional patterns similar to human DN pathogenesis. Notably, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was activated, a phenomenon observed in the early phase of human DN. In addition, metformin improved hyperglycemia and proteinuria in DN zebrafish by modulating AKT phosphorylation. Our results indicated that zMIR/VDBP fish are suitable for elucidating the mechanisms underlying human DN and could be a powerful tool for therapeutic discovery.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping