| First Author | Rockey DC | Year | 2019 |
| Journal | Am J Pathol | Volume | 189 |
| Issue | 11 | Pages | 2209-2220 |
| PubMed ID | 31476284 | Mgi Jnum | J:290804 |
| Mgi Id | MGI:6436793 | Doi | 10.1016/j.ajpath.2019.07.019 |
| Citation | Rockey DC, et al. (2019) Smooth Muscle alpha-Actin Deficiency Leads to Decreased Liver Fibrosis via Impaired Cytoskeletal Signaling in Hepatic Stellate Cells. Am J Pathol 189(11):2209-2220 |
| abstractText | In the liver, smooth muscle alpha-actin (SM alpha-actin) is up-regulated in hepatic stellate cells (HSCs) as they transition to myofibroblasts during liver injury and the wound healing response. Whether SM alpha-actin has specific functional effects on cellular effectors of fibrosis such as HSC is controversial. Here, the relationship between SM alpha-actin and type 1 collagen expression (COL1A1), a major extracellular matrix protein important in liver fibrosis, is investigated with the results demonstrating that knockout of SM alpha-actin leads to reduced liver fibrosis and COL1 expression. The mechanism for the reduction in fibrogenesis in vivo is multifactorial, including not only a reduction in the number of HSCs, but also an HSC-specific reduction in COL1 expression in Acta2-deficient HSCs. Despite a compensatory increase in expression of cytoplasmic beta-actin and gamma-actin isoforms in Acta2(-/-) HSCs, defects were identified in each transforming growth factor beta/Smad2/3 and ET-1/Erk1/2 signaling in Acta2(-/-) HSCs. These data not only suggest a molecular link between the SM alpha-actin cytoskeleton and classic fibrogenic signaling cascades, but also emphasize the relationship between SM alpha-actin and fibrogenesis in hepatic myofibroblasts in vivo. |
