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The Atypical Cyclin-Dependent Kinase 5 (Cdk5) Guards Podocytes from Apoptosis in Glomerular Disease While Being Dispensable for Podocyte Development
- Source :
- Cells, Cells; Volume 10; Issue 9; Pages: 2464, Cells, Vol 10, Iss 2464, p 2464 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Cyclin-dependent kinase 5 (Cdk5) is expressed in terminally differentiated cells, where it drives development, morphogenesis, and survival. Temporal and spatial kinase activity is regulated by specific activators of Cdk5, dependent on the cell type and environmental factors. In the kidney, Cdk5 is exclusively expressed in terminally differentiated glomerular epithelial cells called podocytes. In glomerular disease, signaling mechanisms via Cdk5 have been addressed by single or combined conventional knockout of known specific activators of Cdk5. A protective, anti-apoptotic role has been ascribed to Cdk5 but not a developmental phenotype, as in terminally differentiated neurons. The effector kinase itself has never been addressed in animal models of glomerular disease. In the present study, conditional and inducible knockout models of Cdk5 were analyzed to investigate the role of Cdk5 in podocyte development and glomerular disease. While mice with podocyte-specific knockout of Cdk5 had no developmental defects and regular lifespan, loss of Cdk5 in podocytes increased susceptibility to glomerular damage in the nephrotoxic nephritis model. Glomerular damage was associated with reduced anti-apoptotic signals in Cdk5-deficient mice. In summary, Cdk5 acts primarily as master regulator of podocyte survival during glomerular disease and—in contrast to neurons—does not impact on glomerular development or maintenance.
- Subjects :
- Male
Cell type
QH301-705.5
Cellular differentiation
Biology
p35
Article
Podocyte
Mice
medicine
Animals
Biology (General)
Phosphorylation
Kinase activity
cyclin I
Cells, Cultured
Mice, Knockout
Kidney
Glomerulosclerosis, Focal Segmental
Podocytes
Kinase
Cyclin-dependent kinase 5
apoptosis
Cell Differentiation
Cyclin-Dependent Kinase 5
General Medicine
nephrotoxic nephritis
Phenotype
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
nervous system
proteinuria
Signal Transduction
Subjects
Details
- ISSN :
- 20734409
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....cf73589ab32a89564912ef4b325cf3c7