SMAD4 and Hepatic fibrosis: AMP-activated protein kinase 5 (ARK5) prevents the degradation of TGF-βR I and maternal Smad4 proteins by inhibiting the expression of Smad ubiquitin regulatory factor 2, thereby maintaining TGF-β signal transduction (84, 85), whereas the selective inhibitor HTH-01–015 can target ARK5, reducing carbon tetrachloride (CCl4)-induced liver fibrosis deposition in mice and the expression of fibrosis-related proteins such as α-SMA and type I collagen (Col-1) (86).