β-arrestin-1 drives endothelin-1-mediated podocyte activation and sustains renal injury.

ABSTRACT: Activation of endothelin-A receptor (ET(A)R) by endothelin-1 (ET-1) drives epithelial-to-mesenchymal transition in ovarian tumor cells through β-arrestin signaling. Here, we investigated whether this pathogenetic pathway could affect podocyte phenotype in proliferative glomerular disorders. In cultured mouse podocytes, ET-1 caused loss of the podocyte differentiation marker synaptopodin and acquisition of the mesenchymal marker α-smooth muscle actin. ET-1 promoted podocyte migration via ET(A)R activation and increased β-arrestin-1 expression. Activated ET(A)R recruited β-arrestin-1 to form a trimeric complex with Src leading to epithelial growth factor receptor (EGFR) transactivation and β-catenin phosphorylation, which promoted gene transcription of Snail. Increased Snail expression foste

SUBMITTER: Buelli S 

PROVIDER: S-EPMC3935587 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature