Serine/threonine kinase inhibition as antifibrotic therapy: transforming growth factor-β and Rho kinase inhibitors

Serine/threonine kinases mediate the phosphorylation of intracellular protein targets, transferring a phosphorus group from an adenosine triphosphate molecule to the specific amino acid residues within the target proteins. Serine/threonine kinases regulate multiple key cellular functions. From this large group of kinases, TGF-β through serine/threonine activity of its receptors and Rho kinase (ROCK) play an important role in the development and maintenance of fibrosis in various human diseases, including SSc. In recent years, multiple drugs targeting and inhibiting these kinases have been developed, opening the possibility of becoming potential antifibrotic agents of clinical value for treating fibrotic diseases. This review analyses the contribution of TGF-β and ROCK-mediated serine/threonine kinase molecular pathways to the development and maintenance of pathological fibrosis and the potential clinical use of their inhibition.