Files
Abstract
Because TGF type-1 receptors are the primary mediators in the initiation of myofibroblast differentiation and tissue fibrosis, it appears that which TGF type-1 receptor present in the fibroblasts at a given time will determine the course of myofibroblast development and fibrosis. Literature suggests TGF- type-1 receptors, activin linked kinases 1 and 5 (ALK1 and ALK5) are involved in promoting TGF effects in physiology and pathology. However, the exact TGF type-1 receptor involved in myofibroblast differentiation is still unknown. Our results show that ALK1 is significantly reduced in TGF1 treated fibroblasts with a significant increase in ALK5 expression. Elevated SMA and Akt pathway in TGF1-induced fibroblasts was reduced after the treatment with ALK5 inhibitor. Our data provides the novel molecular insight on the pathogenesis of myofibroblast differentiation and provides much valuable information to develop suitable drugs to prevent fibrosis by pharmacologically targeting the ALK5 receptor.