Calcium signaling induces partial EMT and renal fibrosis in a Wnt4 mCherry knock-in mouse model.

Autor: Naillat F; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland. Electronic address: Florence.naillat@oulu.fi., Deshar G; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland., Hankkila A; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland., Rak-Raszewska A; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland., Sharma A; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland., Prunskaite-Hyyrylainen R; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland., Railo A; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland., Shan J; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland., Vainio SJ; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland; Infotech Oulu, Kvantum Institute, University of Oulu, Finland.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Jun; Vol. 1870 (5), pp. 167180. Date of Electronic Publication: 2024 Apr 21.
DOI: 10.1016/j.bbadis.2024.167180
Abstrakt: The renal tubular epithelial cells (TEC) have a strong capacity for repair after acute injury, but when this mechanism becomes uncontrollable, it leads to chronic kidney diseases (CKD). Indeed, in progress toward CKDs, the TECs may dedifferentiate, undergo epithelial-to-mesenchyme transition (EMT), and promote inflammation and fibrosis. Given the critical role of Wnt4 signaling in kidney ontogenesis, we addressed whether changes in this signaling are connected to renal inflammation and fibrosis by taking advantage of a knock-in Wnt4 mCh/mCh mouse. While the Wnt4 mCh/mCh embryos appeared normal, the corresponding mice, within one month, developed CKD-related phenotypes, such as pro-inflammatory responses including T-cell/macrophage influx, expression of fibrotic markers, and epithelial cell damage with a partial EMT. The Wnt signal transduction component β-catenin remained unchanged, while calcium signaling is induced in the injured TECs involving Nfat and Tfeb transcription factors. We propose that the Wnt4 signaling pathway is involved in repairing the renal injury, and when the signal is overdriven, CKD is established.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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