Overexpression of Corin Ameliorates Kidney fibrosis through Inhibition of Wnt/ β-Catenin Signaling in Mice

Am J Pathol. 2023 Oct 10:S0002-9440(23)00364-4. doi: 10.1016/j.ajpath.2023.09.008. Online ahead of print.ABSTRACTThe Wnt/β-catenin pathway represents a promising therapeutic target for mitigating kidney fibrosis. Corin possesses the homologous ligand binding site (Frizzled-cysteine rich domain, Fz-CRD) similar to Frizzled proteins, which act as receptors for Wnt. The Fz-CRD has been found in eight different proteins, all of which, except for corin, are known to bind Wnt and regulate its signal transmission. It is hypothesized that corin may inhibit the Wnt/β-catenin signaling pathway and thereby reduce fibrogenesis. Reduced expression of corin along with the increased activity of Wnt/β-catenin signaling was found in unilateral ureteral obstruction (UUO) and ischemia/reperfusion injury (UIRI) models. In vitro, corin can bind to the Wnt1 through its Fz-CRDs and inhibit the Wnt1 function responsible for activating β-catenin. TGF-β1 inhibited corin expression, accompanied by activation of β-catenin; conversely, overexpression of corin attenuated the fibrotic effects of TGF-β1. In vivo, adenovirus-mediated overexpression of corin attenuated the progression of fibrosis, which was potentially associated with the inhibition of Wnt/β-catenin signaling and the downregulation of its target genes after UUO and UIRI. These results suggest that corin acts as an antagonist that protects the kidney from pathogenic Wnt/β-catenin signaling and from fibrosis following UUO and UIRI.PMID...
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research