Calcium signaling induces partial EMT and renal fibrosis in a Wnt4mCherry knock-in mouse model
Naillat, Florence; Deshar, Ganga; Hankkila, Anni; Rak-Raszewska, Aleksandra; Sharma, Abhishek; Prunskaite-Hyyrylainen, Renata; Railo, Antti; Shan, Jingdong; Vainio, Seppo J. (2024-05-02)
Naillat, Florence
Deshar, Ganga
Hankkila, Anni
Rak-Raszewska, Aleksandra
Sharma, Abhishek
Prunskaite-Hyyrylainen, Renata
Railo, Antti
Shan, Jingdong
Vainio, Seppo J.
Elsevier
02.05.2024
Naillat, F., Deshar, G., Hankkila, A., Rak-Raszewska, A., Sharma, A., Prunskaite-Hyyrylainen, R., Railo, A., Shan, J., & Vainio, S. J. (2024). Calcium signaling induces partial EMT and renal fibrosis in a Wnt4 knock-in mouse model. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1870(5), 167180. https://doi.org/10.1016/j.bbadis.2024.167180
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202405073172
https://urn.fi/URN:NBN:fi:oulu-202405073172
Tiivistelmä
Abstract
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 Wnt4mCh/mCh mouse. While the Wnt4mCh/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.
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 Wnt4mCh/mCh mouse. While the Wnt4mCh/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.
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