Cytoskeleton-associated protein 4 affects podocyte cytoskeleton dynamics in diabetic kidney disease

Boi R, Lassén E, Johansson A, Liu P, Chaudhari A, Tati R, Müller-Deile J, Schiffer M, Ebefors K, Nyström J (2025)

Publication Type: Journal article

Publication year: 2025

Journal

JCI Insight American Society for Clinical Investigation

Book Volume: 10

Article Number: e181298

Journal Issue: 14

DOI: 10.1172/jci.insight.181298

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 patients with DKD 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.

Authors with CRIS profile

Janina Müller-Deile Department of Medicine 4 – Nephrology and Hypertension Mario Schiffer Lehrstuhl für Innere Medizin IV

Involved external institutions

Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset SE Sweden (SE) AstraZeneca Sweden SE Sweden (SE)

How to cite

APA:

Boi, R., Lassén, E., Johansson, A., Liu, P., Chaudhari, A., Tati, R.,... Nyström, J. (2025). Cytoskeleton-associated protein 4 affects podocyte cytoskeleton dynamics in diabetic kidney disease. JCI Insight, 10(14). https://doi.org/10.1172/jci.insight.181298

MLA:

Boi, Roberto, et al. "Cytoskeleton-associated protein 4 affects podocyte cytoskeleton dynamics in diabetic kidney disease." JCI Insight 10.14 (2025).

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