Hepatic fibrogenesis.
Hepatic fibrogenesis represents a wound-healing response of liver to a variety of insults, ultimately leading to decompensated cirrhosis in many patients and accounting for extensive morbidity and mortality worldwide. The net accumulation of extracellular matrix (ECM) in liver injury arises from increased synthesis by activated hepatic stellate cells and other hepatic fibrogenic cell types, as well as from bone marrow and circulating fibrocytes. Concurrently, degradation of ECM by matrix metalloproteinases (MMPs) fails to keep pace with increased synthesis, in part due to sustained expression of MMP inhibitors (e.g., tissue inhibitors of metalloproteinases). A growing list of circulating, paracrine, and autocrine mediators have been identified that amplify the fibrogenic response of liver. Combined with accelerating knowledge about signaling pathways and genetic determinants, major advances are anticipated in new diagnostics and therapies that will transform the care of patients with chronic liver diseases in the coming years.
Guo
Jinsheng
J
Division of Liver Diseases, Mount Sinai Hospital, Mount Sinai School of Medicine, New York, New York 10029, USA.
Friedman
Scott L
SL
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D015398:Signal Transduction; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D019714:Tissue Inhibitor of Metalloproteinases