A Better Understanding of the Role of TGF-β Family Members in Tissue Fibrosis

Traditionally two different subfamilies of the transforming growth factor-β (TGF-β) superfamily have been associated with different effects on tissue fibrosis: the profibrotic TGF-β subfamily (TGF-β1, TGF-β2 and TGF-β3) and the antifibrotic bone morphogenetic proteins (BMPs) subfamily. TGF-β1 is the most widely studied profibrotic cytokine, as it regulates numerous processes involved in tissue fibrosis: synthesis of extracellular matrix proteins (ECM), apoptosis of the parenchymal cells, regulation of epithelial-tomesenchymal transition (EMT) and endothelial-to-mesenchymal transition [1,2]. On the other hand, BMPs (especially BMP7) have been considered as antifibrotic proteins [2-4]. TGF-β subfamily members activate ALK5 type I receptors –thus activating Smad2 and Smad3 proteinswhereas BMPs activate ALK1, ALK2, ALK3 and ALK6 receptors and thus activating Smad1, Smad5 and Smad8 proteins.