Hepatic lipocytes, TIMP-1 and liver fibrosis.
In progressive liver fibrosis, the rate [corrected] of extracellular collagen deposition exceeds its rate of degradation. Collagen and related proteins are synthesised in the fat-storing liver cells (lipocytes). When injured, these cells proliferate and change into myofibroblast-like cells, secreting even more collagen into the extracellular space. The degradation of collagen is accomplished by metalloproteinases, whose activity is reduced by tissue inhibitors (TIMPs). Injured lipocytes produce an excess of these inhibitors. The final result of lipocyte injury is thus progressive liver fibrosis. There is evidence that TIMPs also play a role in progressive fibrosis in other tissues.
Arthur
M J
MJ
University Medicine, Southampton General Hospital.
Iredale
J P
JP
D000818:Animals; D002478:Cells, Cultured; D017364:Collagenases / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000201:enzymology / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000502:physiology*; D013379:Substrate Specificity; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D008666:Metalloendopeptidases