TGF-β signals through both canonical (Smad-based) and non-canonical (non-Smad-based) pathways; Smad-based TGF-β signaling plays a central role in the development of renal fibrosis; non-Smad-based profibrotic actions of TGF-β signaling are regulated by interactions with other signaling pathways (e.g., MAPK/ERK and PI3K/AKT pathways signaling) [15]. This evidence concerns the gene TGFB1 and renal fibrosis.