title: Pathogenesis of liver fibrosis.
abstract: 1. Liver fibrosis is a common sequel to diverse liver injuries. It is characterized by an accumulation of interstitial collagens and other matrix components. The hepatic stellate cell is pivotal to the pathogenic process. Fibrotic liver injury results in activation of the hepatic stellate cell which undergoes a phenotypic change to a proliferative myofibroblast-like cell which synthesizes excess interstitial collagens and other matrix components. 2. The process of initiation of activation and its perpetuation result from complex, often interrelated series of signalling mechanisms which converge on this effector cell. Such mechanisms include alterations in matrix resulting in changed cell-matrix interactions and stimulation by cytokines released from damaged hepatocytes, infiltrating inflammatory cells, Kupffer cells and matrix. Foremost among the profibrotic cytokines is transforming growth factor beta 1. 3. Once the hepatic stellate cell is activated the preceding matrix changes and recurrent injurious stimuli will perpetuate the activated state. 4. Despite the accumulation of excess collagens, the liver retains a capacity for matrix degradation. This capacity may be overwhelmed and any secreted matrix remodelling enzymes may be inhibited by the concurrently secreted tissue inhibitors of metallo-proteinase-1 and alpha 2-macroglobulin. 5. Our understanding of the molecular pathogenesis of liver fibrosis is increasing. It is anticipated that this knowledge will provide novel therapeutic avenues to treat this disease process.
authors.forename: R
authors.initials: R
authors.lastname: Alcolado
authors.forename: M J
authors.initials: MJ
authors.lastname: Arthur
authors.forename: J P
authors.initials: JP
authors.lastname: Iredale
mesh_terms: D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000293:injuries* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D003094:Collagen