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Semin Liver Dis 2007; 27(4): 413-426
DOI: 10.1055/s-2007-991517
DOI: 10.1055/s-2007-991517
Hepatic Fibrogenesis
Further Information
Publication History
Publication Date:
02 November 2007 (online)
ABSTRACT
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.
KEYWORDS
Hepatic fibrogenesis - extracellular matrix - hepatic stellate cells - tissue inhibitors of metalloproteinases - signaling pathways
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Scott L FriedmanM.D.
Division of Liver Diseases, Mount Sinai School of Medicine
Box 1123, 1425 Madison Avenue, Room 1170C, New York, NY 10029
Email: scott.friedman@mssm.edu