CTGF公司
纤维化
化学
细胞外基质
癌症研究
表皮生长因子受体
生长因子
体内
肾
表皮生长因子
表皮生长因子受体抑制剂
药理学
细胞生物学
受体
内科学
病理
生物化学
医学
生物
生物技术
作者
Jiale Dong,Jing Xiao,Jianyi Li,Haohui Yu,Qian Zhao,Qinglin Tang,Hui Chen,Han Li,Kaili Wu,Jinping Lei,Rui Wang,Xianxing Jiang
标识
DOI:10.1021/acs.jmedchem.3c00594
摘要
Kidney fibrosis is a serious consequence of chronic kidney disease (CKD), and currently, there is no effective pharmacological treatment available. Cellular communication network-2 (CCN2/CTGF) is an extracellular matrix (ECM) protein that regulates the fibrotic process by activating the epidermal growth factor receptor (EGFR) signaling pathway. We herein present the discovery and structure-activity relationship study of novel peptides targeting CCN2 to develop potent and stable specific inhibitors of the CCN2/EGFR interaction. Remarkably, the 7-mer cyclic peptide OK2 exhibited potent activities to inhibit CCN2/EGFR-induced STAT3 phosphorylation and cellular ECM protein synthesis. Subsequent in vivo studies demonstrated that OK2 significantly alleviated renal fibrosis in a unilateral ureteral obstruction (UUO) mouse model. Moreover, this study first revealed that the peptide candidate could efficiently block CCN2/EGFR interaction through binding to the CT domain of CCN2, providing a new alternative strategy for peptide-based targeting of CCN2 and modulating CCN2/EGFR-mediated biological functions in kidney fibrosis.
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