Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced liver fibrosis is generally considered to be irreversible. We studied the reversibility of marked liver fibrosis in rabbits infected with Schistosoma japonicum. We determined liver collagen content, collagen biosynthesis, and collagenase activity using serial biopsy specimens obtained 20, 40, and 60 weeks after infection. Reversibility of this process was investigated in rabbits cured of infection at 21 weeks; control rabbits not cured of infection were also studied. At 20 weeks, liver collagen content was 16-fold greater than normal, with accumulation of collagen types I, III, and V. Synthesis of collagen within fibrotic liver slices was 10-fold greater than normal. Liver collagenolytic activity for a type I substrate was 19-fold greater than normal. After parasitologic cure, a striking morphologic reversal of fibrosis occurred during the subsequent 40 weeks, with the return of liver collagen content to three-fold greater than normal and a 75% decrease in synthetic rates compared with those at 20 weeks (P < 0.01). Collagenolytic activity remained elevated to the same degree noted at 20 weeks. A similar but lesser resolution of fibrosis also occurred in untreated control rabbits, coincident with a spontaneous decrease in new egg deposition known to occur in this model system. We conclude that advanced liver fibrosis in S. japonicum-infected rabbits is slowly reversible after cure or senescence of the infection. A possible mechanism for this reversal is persistently increased collagenolysis as collagen synthesis diminishes.
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PMID:Reversal of advanced liver fibrosis in rabbits with Schistosomiasis japonica. 816 57

A novel method for the isolation of schistosome eggs and miracidia from livers of mice infected with Schistosoma japonicum or S. mansoni is described. The method employed collagenase B to degrade the interstitial matrix of mouse liver tissue, after which the schistosome eggs were separated from the liver cells by 2 single-step density centrifugations through Percoll. Using this procedure sufficient quantities of miracidia were obtained to generate a cDNA library. Southern blot analysis demonstrated that miracidia isolated by this method were free from contaminating host DNA.
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PMID:A method for the isolation of schistosome eggs and miracidia free of contaminating host tissues. 922 54

The disease manifestations of schistosomiasis arise from the mammalian host-mediated type 2 T-helper cell-induced (Th2) fibro-granulomatous inflammatory response to eggs trapped within host tissues. Activated hepatic stellate cells are well described as the effector cells of hepatic fibrosis in a variety of human diseases and rodent models. The aim of this study was to further understand the mechanism of fibrosis and the role of hepatic stellate cells in hepatic schistosomiasis progression. Groups of female CBA mice, which produce an intermediate degree of Schistosoma japonicum-induced liver fibrosis, were infected with S. japonicum, perfused at fortnightly time points and the liver tissue and contained egg granulomas examined by immunohistochemistry and cytokine and chemokine analysis using quantitative PCR. Immunohistochemistry demonstrated the presence of activated hepatic stellate cells in the periphery of egg granulomas, adjacent to fibrotic areas. Time course analysis demonstrated that the transcription of smooth muscle actin-alpha type 1 collagen, IL-4, IL-13, IL-13Ralpha2 and tissue inhibitor of metalloproteinase-1 mirrored the initial increase and subsequent down-modulation of granuloma diameter in mice. However, the transcription of monocyte chemo-attractant protein-1, Regulated upon Activation Normal T Cell Expressed and Secreted (RANTES), TNF-alpha, IFN-gamma and matrix metalloproteinase-9 paralleled the evolution of the total liver disease burden. Transforming growth factor-beta1 transcription did not appear to be of biological significance in this mouse model. Immunohistochemical analysis of human hepatic granulomas showed close association of smooth muscle actin-alpha-expressing cells with fibrosis in five available cases of end-stage (advanced) schistosomiasis japonica. We conclude that activated hepatic stellate cells play a contributory role in the granulomatous, fibrotic process induced by S. japonicum eggs, both in the murine model and in human disease.
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PMID:A contributory role for activated hepatic stellate cells in the dynamics of Schistosoma japonicum egg-induced fibrosis. 1680 22