微泡
外体
CD44细胞
骨桥蛋白
成纤维细胞
细胞生物学
连环素
纤维化
癌症研究
化学
生物
细胞
医学
内科学
细胞培养
信号转导
小RNA
基因
生物化学
Wnt信号通路
遗传学
作者
Shuangqin Chen,Meijia Zhang,Jiemei Li,Jiewu Huang,Shi‐Ping Zhou,Xin Hou,Huiyun Ye,Xi Liu,Shaowei Xiang,Weiwei Sui,Jinhua Miao,Fan Fan Hou,Youhua Liu,Lili Zhou
摘要
Tubular injury and peripheral fibroblast activation are the hallmarks of chronic kidney disease (CKD), suggesting intimate communication between the two types of cells. However, the underlying mechanisms remain to be determined. Exosomes play a role in shuttling proteins and other materials to recipient cells. In our study, we found that exosomes were aroused by β-catenin in renal tubular cells. Osteopontin (OPN), especially its N-terminal fragment (N-OPN), was encapsulated in β-catenin-controlled tubular cell-derived exosome cargo, and subsequently passed to fibroblasts. Through binding with CD44, exosomal OPN promoted fibroblast proliferation and activation. Gene deletion of β-catenin in tubular cells (Ksp-β-catenin-/- ) or gene ablation of CD44 (CD44-/- ) greatly ameliorated renal fibrosis. Notably, N-OPN was carried by exosome and secreted into the urine of patients with CKD, and negatively correlated with kidney function. The urinary exosomes from patients with CKD greatly accelerated renal fibrosis, which was blocked by CD44 deletion. These results suggest that exosome-mediated activation of the OPN/CD44 axis plays a key role in renal fibrosis, which is controlled by β-catenin.
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