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Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
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Increased dynamin expression precedes proteinuria in glomerular disease
Ramzi Khalil1, Klaas Koop1, Reinhold Kreutz2
1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
The Journal of Pathology
|October 24, 2018
Summary
Dynamin is crucial for kidney filtration barrier integrity. Increased dynamin expression in proteinuric kidney disease suggests a compensatory mechanism, highlighting its potential as a therapeutic target for chronic kidney disease.
Area of Science:
- Nephrology
- Cell Biology
- Pathology
Background:
- Dynamin is vital for glomerular filtration barrier function, regulating podocyte actin cytoskeleton and nephrin turnover.
- Reduced dynamin expression leads to proteinuria, indicating its critical role in kidney health.
- Dynamin is a potential therapeutic target for chronic kidney disease (CKD).
Purpose of the Study:
- To investigate the pathophysiological role of dynamin in proteinuric conditions in rat and human models.
- To determine dynamin's expression patterns in spontaneous and induced proteinuria.
- To explore dynamin's involvement in human proteinuric kidney diseases.
Main Methods:
- Examined glomerular Dnm1 and Dnm2 mRNA levels in a rat model of spontaneous proteinuria.
- Investigated the effect of dynamin knockdown on proteinuria in zebrafish embryos.
- Assessed glomerular dynamin and cathepsin L protein expression in human proteinuric kidney diseases.
Main Results:
- Glomerular Dnm1 and Dnm2 mRNA levels increased before proteinuria onset in rats.
- Dynamin knockdown in zebrafish embryos resulted in proteinuria.
- Elevated glomerular dynamin and cathepsin L protein expression observed in human proteinuric kidney diseases.
Conclusions:
- Increased glomerular dynamin expression may represent an exhausted attempt to maintain barrier integrity.
- Dynamin plays a significant role in maintaining the glomerular filtration barrier.
- Dynamin is a promising therapeutic target for proteinuric kidney diseases.
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