Crosstalk of injured podocytes with parietal epithelial cells through Wnt4/β-Catenin signaling

Schwartze E, Pfister E, Endlich N, Endlich T, Amann KU, Büttner-Herold M, Pippin J, Shankland SJ, Daniel C (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 15

Article Number: 19652

Journal Issue: 1

DOI: 10.1038/s41598-025-04092-3

Abstract

Focal segmental glomerular sclerosis (FSGS) is considered an irreversible lesion in kidney disease. Here, we investigated the role of the wnt4/β-Catenin signaling pathway in FSGS lesion formation and the crosstalk between PECs and podocytes in a transgenic FSGS rat model and human primary FSGS to explore potential sex-specific differences and therapeutic options. After model induction in rats, we observed strong podocytes loss on day 7, which was significantly higher in male than in female rats. Starting at d14, both glomerular mRNA and protein expression of Wnt4 were increased, but more pronounced in males. Wnt4 was localized to podocytes and β-Catenin to Pax8-positive lesions. The Wnt4 target gene CD44 was strongly upregulated on d7 and increased until the end of the experiment (d42). In cell culture, we confirmed that injured podocytes expressed and secreted Wnt4, which stimulated the expression of the Wnt target gene Axin2 in PECs but not in podocytes. Wnt4/β-Catenin pathway activation was confirmed in human biopsies with podocytopathic FSGS. In conclusion, the canonical Wnt/β-Catenin axis plays a critical role in the crosstalk between PECs and injured podocytes. Furthermore, sex-specific differences in podocyte injury and regeneration appear to be, at least in part, Wnt4-mediated.

Authors with CRIS profile

Eike Schwartze Department of Nephropathology Kerstin Ute Amann Professur für Nephropathologie Maike Büttner-Herold Department of Nephropathology Christoph Daniel Department of Nephropathology

Involved external institutions

NIPOKA GmbH DE Germany (DE) University of Washington US United States (USA) (US)

How to cite

APA:

Schwartze, E., Pfister, E., Endlich, N., Endlich, T., Amann, K.U., Büttner-Herold, M.,... Daniel, C. (2025). Crosstalk of injured podocytes with parietal epithelial cells through Wnt4/β-Catenin signaling. Scientific Reports, 15(1). https://doi.org/10.1038/s41598-025-04092-3

MLA:

Schwartze, Eike, et al. "Crosstalk of injured podocytes with parietal epithelial cells through Wnt4/β-Catenin signaling." Scientific Reports 15.1 (2025).

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