PUBLICATION
Cytoskeleton-associated protein 4 (CKAP4) affects podocyte cytoskeleton dynamics in diabetic kidney disease
- Authors
- Boi, R., Lassén, E., Johansson, A., Liu, P., Chaudhari, A., Tati, R., Müller-Deile, J., Schiffer, M., Ebefors, K., Nyström, J.
- ID
- ZDB-PUB-250611-2
- Date
- 2025
- Source
- JCI insight : (Journal)
- Registered Authors
- Keywords
- Cell biology, Chronic kidney disease, Cytoskeleton, Integrins, Nephrology
- MeSH Terms
-
- Gene Knockdown Techniques
- Integrins/metabolism
- Cytoskeleton*/metabolism
- Cytoskeletal Proteins*/genetics
- Cytoskeletal Proteins*/metabolism
- Female
- Humans
- Zebrafish
- Podocytes*/metabolism
- Podocytes*/pathology
- Male
- Animals
- Diabetic Nephropathies*/genetics
- Diabetic Nephropathies*/metabolism
- Diabetic Nephropathies*/pathology
- PubMed
- 40493405 Full text @ JCI Insight
Citation
Boi, R., Lassén, E., Johansson, A., Liu, P., Chaudhari, A., Tati, R., Müller-Deile, J., Schiffer, M., Ebefors, K., Nyström, J. (2025) Cytoskeleton-associated protein 4 (CKAP4) affects podocyte cytoskeleton dynamics in diabetic kidney disease. JCI insight. :.
Abstract
Podocytes are kidney glomerular cells that depend on rigorously regulated cytoskeleton components and integrins to form and maintain the so-called foot processes, apparatuses that attach podocytes to the glomerular basement membrane and connect them to neighboring podocytes. In diabetic kidney disease (DKD) these foot processes are effaced as a result of cytoskeleton dysregulation, a phenomenon that gradually reduces glomerular filtration. Cytoskeleton-associated protein 4 (CKAP4) is a known linker between the endoplasmic reticulum, integrins and microtubular cytoskeleton. Since CKAP4 gene expression is downregulated in glomeruli from DKD patients but not in other chronic kidney diseases, we hypothesized a role for CKAP4 in the mechanisms leading to foot process effacement (FPE) in DKD. CKAP4 mRNA reduction in podocytes in DKD was demonstrated in human kidney biopsies. Knockdown of CKAP4 in vivo in zebrafish resulted in edema, proteinuria and foot process effacement, all typical features of DKD. Knockdown of CKAP4 in vitro led to disruption of the actin cytoskeleton and of the microtubular orientation. Moreover, it caused a downregulation of several integrins. These findings indicate that CKAP4 is crucial for foot process dynamics of podocytes. Its reduction, unique to DKD, is mechanistically connected to the pathophysiological processes leading to podocyte FPE.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping