β-catenin-controlled tubular cell-derived exosomes play a key role in fibroblast activation via the OPN-CD44 axis.

ABSTRACT: 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 a

SUBMITTER: Chen S 

PROVIDER: S-EPMC8936047 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature