Calcium signaling induces partial EMT and renal fibrosis in a Wnt4 < sup > mCherry < /sup > knock-in mouse model

Biochim Biophys Acta Mol Basis Dis. 2024 Apr 21:167180. doi: 10.1016/j.bbadis.2024.167180. Online ahead of print.ABSTRACTThe 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.PMID:38653356 | DOI:10.1016/j.bbadis.2024.167180

Source: Biochimica et Biophysica Acta - April 23, 2024 Category: Biochemistry Authors: Florence Naillat Ganga Deshar Anni Hankkila Aleksandra Rak-Raszewska Abhishek Sharma Renata Prunskaite-Hyyrylainen Antti Railo Jingdong Shan Seppo J Vainio Source Type: research