PUBLICATION
Increased dynamin expression precedes proteinuria in glomerular disease
- Authors
- Khalil, R., Koop, K., Kreutz, R., Spaink, H.P., Hogendoorn, P.C.W., Bruijn, J.A., Baelde, H.J.
- ID
- ZDB-PUB-181024-7
- Date
- 2018
- Source
- The Journal of pathology 247(2): 177-185 (Journal)
- Registered Authors
- Spaink, Herman P.
- Keywords
- Dynamin, histology, kidney glomerulus, proteinuria, rats, zebrafish
- MeSH Terms
-
- Adult
- Aged
- Animals
- Cathepsin L/genetics
- Cathepsin L/metabolism
- Disease Models, Animal
- Dynamin I/genetics
- Dynamin I/metabolism*
- Dynamin II/genetics
- Dynamin II/metabolism*
- Female
- Glomerular Filtration Rate
- Humans
- Kidney Diseases/genetics
- Kidney Diseases/metabolism*
- Kidney Diseases/physiopathology
- Kidney Glomerulus/metabolism*
- Kidney Glomerulus/physiopathology
- Male
- Middle Aged
- Proteinuria/genetics
- Proteinuria/metabolism*
- Proteinuria/physiopathology
- Rats, Inbred Dahl
- Rats, Inbred SHR
- Time Factors
- Up-Regulation
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 30350425 Full text @ J. Pathol.
Citation
Khalil, R., Koop, K., Kreutz, R., Spaink, H.P., Hogendoorn, P.C.W., Bruijn, J.A., Baelde, H.J. (2018) Increased dynamin expression precedes proteinuria in glomerular disease. The Journal of pathology. 247(2):177-185.
Abstract
Dynamin plays an essential role in maintaining the structure and function of the glomerular filtration barrier. Specifically, dynamin regulates the actin cytoskeleton and the turnover of nephrin in podocytes, and knocking down dynamin expression causes proteinuria. Moreover, promoting dynamin oligomerization with Bis-T-23 restores podocyte function and reduces proteinuria in several animal models of chronic kidney disease. Thus, dynamin is a promising therapeutic target for treating chronic kidney disease. Here, we investigated the pathophysiological role of dynamin under proteinuric circumstances in a rat model and in humans. We found that glomerular Dnm2 and Dnm1 mRNA levels are increased prior to the onset of proteinuria in a rat model of spontaneous proteinuria. Also, in zebrafish embryos we confirm that knocking down dynamin translation results in proteinuria. Finally, we show that the glomerular expression of dynamin and cathepsin L protein is increased in several human proteinuric kidney diseases. We propose that the increased expression of glomerular dynamin reflects an exhausted attempt to maintain and/or restore integrity of the glomerular filtration barrier. These results confirm that dynamin plays an important role in maintaining the glomerular filtration barrier, and they support the notion that dynamin is a promising therapeutic target in proteinuric kidney disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping