Open Accessβ‐catenin‐controlled tubular cell‐derived exosomes play a key role in fibroblast activation via the OPN‐CD44 axis
Author(s) -
Chen Shuangqin,
Zhang Meijia,
Li Jiemei,
Huang Jiewu,
Zhou Shan,
Hou Xiaotao,
Ye Huiyun,
Liu Xi,
Xiang Shaowei,
Shen Weiwei,
Miao Jinhua,
Hou Fan Fan,
Liu Youhua,
Zhou Lili
Publication year - 2022
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1002/jev2.12203
Subject(s) - microvesicles , cd44 , exosome , osteopontin , fibroblast , catenin , cancer research , fibrosis , microbiology and biotechnology , chemistry , biology , cell , medicine , cell culture , signal transduction , microrna , gene , biochemistry , wnt signaling pathway , genetics
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.