Mesothelial cells give rise to hepatic stellate cells and myofibroblasts via mesothelial-mesenchymal transition in liver injury.
In many organs, myofibroblasts play a major role in the scarring process in response to injury. In liver fibrogenesis, hepatic stellate cells (HSCs) are thought to transdifferentiate into myofibroblasts, but the origins of both HSCs and myofibroblasts remain elusive. In the developing liver, lung, and intestine, mesothelial cells (MCs) differentiate into specific mesenchymal cell types; however, the contribution of this differentiation to organ injury is unknown. In the present study, using mouse models, conditional cell lineage analysis has demonstrated that MCs expressing Wilms tumor 1 give rise to HSCs and myofibroblasts during liver fibrogenesis. Primary MCs, isolated from adult mouse liver using antibodies against glycoprotein M6a, undergo myofibroblastic transdifferentiation. Antagonism of TGF-β signaling suppresses transition of MCs to mesenchymal cells both in vitro and in vivo. These results indicate that MCs undergo mesothelial-mesenchymal transition and participate in liver injury via differentiation to HSCs and myofibroblasts.
Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis and Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA.
Yuchang
Y
Li
Jiaohong
J
Wang
Kinji
K
Asahina
D000818:Animals; D001659:Biliary Tract / Q000378:metabolism / Q000473:pathology; D002251:Carbon Tetrachloride / Q000633:toxicity; D019070:Cell Lineage; D054338:Cell Transdifferentiation / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration; D008562:Membrane Glycoproteins / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism
C083480:Gpm6a protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D025721:WT1 Proteins; D002251:Carbon Tetrachloride