Mechanisms of hepatic fibrogenesis

• Published in: Baillière's best practice & research. Clinical gastroenterology Vol. 25; no. 2; pp. 195 - 206
• Main Authors: Lee, Ursula E., Friedman, Scott L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.04.2011; Elsevier Limited
• Subjects: Adipokines; Angiogenesis; Animals; Apoptosis; Chemokines; Cytokines; Epidermal growth factor; Fibrogenesis; Gastroenterology and Hepatology; Genotype & phenotype; Growth factors; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - pathology; Humans; Immune cells; Immune system; Kinases; Liver Cirrhosis - genetics; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Phosphorylation; Rodents; Signal Transduction - genetics; Stellate cell; Tyrosine kinase; Wound healing; Tyrosine kinase; Stellate cell; Immune cells; Adipokines; Growth factors; Fibrogenesis
• ISSN: 1521-6918; 1532-1916; 1532-1916
• DOI: 10.1016/j.bpg.2011.02.005

Multiple etiologies of liver disease lead to liver fibrosis through integrated signaling networks that regulate the deposition of extracellular matrix. This cascade of responses drives the activation of hepatic stellate cells (HSCs) into a myofibroblast-like phenotype that is contractile, proliferative and fibrogenic. Collagen and other extracellular matrix (ECM) components are deposited as the liver generates a wound-healing response to encapsulate injury. Sustained fibrogenesis leads to cirrhosis, characterized by a distortion of the liver parenchyma and vascular architecture. Uncovering the intricate mechanisms that underlie liver fibrogenesis forms the basis for efforts to develop targeted therapies to reverse the fibrotic response and improve the outcomes of patients with chronic liver disease.