Figure 1.

TGF-β and BMP-7 pathways. The TGF-β pathway is shown in its canonical and non-canonical forms. The canonical pathway is Smad-dependent, in which the TGF-β binds to the TGF-βRI and promotes a phosphorylation of TGF-βRII, which will posteriorly recruit downstream signals that results in the phosphorylation of both Smad2 and Smad3 to form a trimer complex with the Smad 4, a common Smad. This results in the trimer translocation into the nucleus and the activation of a number of genes related to cellular functions and profibrotic effect including EMT, cell growth, and apoptosis. The non-canonical pathway, also known as the non-Smad signaling pathways, is mediated by other transducers, such as the p38 mitogen-activated protein kinase (P38MAPK) pathways, that includes each of the extracellular signal regulated kinases (ERKs), AKT, c-Jun amino terminal kinase (JNK), Rho family GTPases, as well as the IkB kinase (IKK), and phosphatidylinositol-3 kinase (PI3K). The non-canonical pathway results in different cellular functions and can amplify the Smad pathway. The BMP-7 pathway is activated after the binding of BMP-7 to the BMP-7R complex and results in the phosphorylation of the Smad1/5/8 to form a complex with the common Smad4 and translocate in the nucleus to activate the opposing function to TGF-β, creating a normal physiological balance between the TGF-β pathway, ultimately leading to an antifibrotic effect, increasing ECM degradation and inducing MET.