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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombin inhibition protects against liver fibrosis. However, it is not known whether the thrombin profibrogenic effect is due to effects on blood coagulation or to signaling via protease-activated receptors (PARs). We took advantage of the lack of blood coagulation defects in PAR-1-knockout mice. Acute carbon tetrachloride (CCl(4)) toxicity was similar in wild-type (WT), PAR-1(-/-), and PAR-1(+/-) mice as judged by aminotransferase levels, area of liver necrosis, and liver peroxidation measured by Fourier-transformed infrared spectroscopy. Fifteen mice/group received CCl(4) or its solvent for 6 wk (300 microl/kg, 3 times a week). Fibrosis area was increased 10-fold by CCl(4) treatment in WT mice. PAR-1 deficiency protected against fibrosis, with 36% and 56% decrease in PAR-1(+/-) and PAR-1(-/-) mice, respectively (P < 0.001). Similar results were obtained for area of activated fibrogenic cells (64% and 79% decrease in PAR-1(+/-) and PAR-1(-/-) mice, respectively, P < 0.001). These findings were corroborated by measurements of type I collagen, matrix metalloproteinase-2, and PDGF-beta receptor mRNA levels. There was also a significant decrease in T lymphocyte infiltration in PAR-1-deficient mice. Altogether, these results suggest that thrombin profibrogenic effects are independent of effects on blood coagulation and are instead due to direct effects on fibrogenic cells and possibly on T lymphocytes.
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PMID:Protease-activated receptor 1 knockout reduces experimentally induced liver fibrosis. 1796 54

Cirrhosis is a pathological entity characterized by the association of hepatocyte necrosis, fibrosis and regenerative nodules; hemodynamic and neurohormonal metabolic factors intervening in its development mechanisms, resulting in hepatic stellate cell activation and transformation and development of liver fibrosis. Cytokines are key modulators of liver cell fibroblast transformation. Prostaglandins play an important role in the control of vascular tone and in thrombosis; Angiotensin II stimulates fibroblast proliferation by AT-1 receptors. Thrombin influences cellular remodeling in the liver and cardiovascular cirrhotic patients. Oxidative stress is involved in the development of liver cirrhosis by primary and secondary biological irreversible effects. Complex etiology involving vasoactive substances, oxidative stress in the pathogenesis of liver cirrhosis, require further studies to elucidate the mechanisms involved in hemodynamic disturbances associated with this disorder.
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PMID:Involvement of vasoactive substances in hemodynamics disturbances in cirrhosis. 2587 Jun 93