Rockey DC, et al. - Researchers focused on the association between smooth muscle α-actin (SM α-actin) and type 1 collagen expression (COL1A1), a major extracellular matrix protein significant in liver fibrosis and illustrated that knockout of SM α-actin results in decreased liver fibrosis and COL1 expression. The mechanism for the decrease in fibrogenesis in vivo is multifactorial, including not only a decline in the number of hepatic stellate cells (HSCs) but also HSC specific decrease in COL1 expression in Acta2 deficient HSCs. Irrespective of a compensatory rise in expression of cytoplasmic β-actin and γ-actin isoforms in Acta2^-/- HSCs, defects were recognized in each transforming growth factor-beta/Smad2/3 and ET-1/Erk1/2 signaling in Acta2^-/- HSCs. Thus, these data not only suggest a molecular link between the SM α-actin cytoskeleton and classic fibrogenic signaling cascades however, it also highlights the correlation between SM α-actin and fibrogenesis in hepatic myofibroblasts in vivo.