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.
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
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping