Cyclosporine A inhibits MRTF-SRF signaling through Na⁺/K⁺ ATPase inhibition and actin remodeling.

ABSTRACT: Calcineurin inhibitors (CNI) are the pillars of immunosuppression in transplantation. However, they display a potent nephrotoxicity whose mechanisms remained widely unsolved. We used an untargeted quantitative proteomic approach (iTRAQ technology) to highlight new targets of CNI in renal proximal tubular cells (RPTCs). CNI-treated RPTCs proteome displayed an over-representation of actin-binding proteins with a CNI-specific expression profile. Cyclosporine A (CsA) induced F-actin remodeling and depolymerization, decreased F-actin-stabilizing, polymerization-promoting cofilin (CFL) oligomers, and inhibited the G-actin-regulated serum response factor (SRF) pathway. Inhibition of CFL canonical phosphorylation pathway reproduced CsA effects; however, S3-R, an analogue of the phosphorylation sit

SUBMITTER: Burat B 

PROVIDER: S-EPMC6996406 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature