WNT/?-Catenin Signaling Promotes TGF-?-Mediated Activation of Human Cardiac Fibroblasts by Enhancing IL-11 Production

Cardiac fibrosis is a pathological process associated with the development of heart failure. TGF-? and WNT signaling have been implicated in pathogenesis cardiac fibrosis, however, little known about molecular cross-talk between these two pathways. The aim this study was to examine effect exogenous canonical WNT3a non-canonical WNT5a TGF-?-activated human fibroblasts. We found that induced ?-catenin-dependent response, whereas prompted AP-1 activity. triggered profibrotic signatures fibroblasts, co-stimulation or co-activation ?-catenin pathway GSK3? inhibitor CHIR99021 enhanced collagen I fibronectin production active contractile stress fibers. In absence TGF-?, neither nor exerted responses. On level, phosphorylation TAK1 secretion IL-11 but showed no on Smad pathway. Neutralization activity blocking anti-IL-11 antibody effectively reduced response fibroblasts activated WNT3a. contrast WNT3a, suppressed TGF-?-induced I. conclusion, WNT/?-catenin promotes TGF-?-mediated fibroblast-to-myofibroblast transition by enhancing production. Thus, uncovered mechanism broadens our knowledge basis fibrogenesis defines novel therapeutic targets for fibrotic diseases.