Non-canonical (non-SMAD2/3) TGF-β signaling in fibrosis: Mechanisms and targets

Transforming growth factor (TGF)-beta uses several intracellular signaling pathways besides canonical ALK5-Smad2/3 signaling to regulate a diverse array of cellular functions. Several of these so-called non-canonical (non-Smad2/3) pathways have been implicated in the pathogenesis of fibrosis and may therefore represent targets for therapeutic intervention. This review summarizes our current knowledge on the mechanisms of noncanonical TGF-beta signaling in fibrosis, the potential molecular targets and the use of agonists/antagonists for therapeutic intervention.