Wnt信号通路
干瘪的
纤维化
信号转导
连环素
细胞生物学
LRP6型
癌症研究
LRP5
WNT3A型
肾
连环蛋白
化学
内分泌学
内科学
生物
医学
作者
Xiaole Su,Sijia Li,Yanru Zhang,X. Tie,Rongrong Feng,Xiaojiao Guo,Xi Qiao,Lihua Wang
标识
DOI:10.1016/j.ajpath.2023.09.008
摘要
The 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. We 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 ureteral ischemia/reperfusion injury (UIRI) models. In vitro, corin bound to the Wnt1 through its Fz-CRDs and inhibit the Wnt1 function responsible for activating β-catenin. Transforming growth factor-β1 inhibited corin expression, accompanied by activation of β-catenin; conversely, overexpression of corin attenuated the fibrotic effects of transforming growth factor-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 down-regulation 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI