{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T15:06:28Z","timestamp":1768835188682,"version":"3.49.0"},"reference-count":37,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p>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<jats:sub>4<\/jats:sub>) toxicity was similar in wild-type (WT), PAR-1<jats:sup>\u2212\/\u2212<\/jats:sup>, and PAR-1<jats:sup>+\/\u2212<\/jats:sup>mice as judged by aminotransferase levels, area of liver necrosis, and liver peroxidation measured by Fourier-transformed infrared spectroscopy. Fifteen mice\/group received CCl<jats:sub>4<\/jats:sub>or its solvent for 6 wk (300 \u03bcl\/kg, 3 times a week). Fibrosis area was increased 10-fold by CCl<jats:sub>4<\/jats:sub>treatment in WT mice. PAR-1 deficiency protected against fibrosis, with 36% and 56% decrease in PAR-1<jats:sup>+\/\u2212<\/jats:sup>and PAR-1<jats:sup>\u2212\/\u2212<\/jats:sup>mice, respectively ( P &lt; 0.001). Similar results were obtained for area of activated fibrogenic cells (64% and 79% decrease in PAR-1<jats:sup>+\/\u2212<\/jats:sup>and PAR-1<jats:sup>\u2212\/\u2212<\/jats:sup>mice, respectively, P &lt; 0.001). These findings were corroborated by measurements of type I collagen, matrix metalloproteinase-2, and PDGF-\u03b2 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.<\/jats:p>","DOI":"10.1152\/ajpgi.00444.2007","type":"journal-article","created":{"date-parts":[[2007,10,25]],"date-time":"2007-10-25T23:19:52Z","timestamp":1193354392000},"page":"G226-G235","source":"Crossref","is-referenced-by-count":57,"title":["Protease-activated receptor 1 knockout reduces experimentally induced liver 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