{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T02:19:52Z","timestamp":1769912392012,"version":"3.49.0"},"reference-count":41,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:p>\n                    <jats:bold>Background\/Aim:<\/jats:bold>\n                    Several lines of evidence incriminate the serine proteinase thrombin in liver fibrogenesis either through its procoagulant function or its signaling via cell-surface receptors. The aim of this study was therefore to evaluate the effect of thrombin inhibition on experimental liver fibrosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Fibrosis was induced in rats by administration of CCl\n                    <jats:sub>4<\/jats:sub>\n                    for either three or seven weeks. Oral administration of the thrombin antagonist SSR182289 started one week after the start of CCl\n                    <jats:sub>4<\/jats:sub>\n                    intoxication. Fibrosis and the area occupied by alpha smooth muscle actin (ASMA) positive cells were quantified with histomorphometry. Expression of fibrosis related genes was measured by real time RT-PCR.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    After three weeks of CCl\n                    <jats:sub>4<\/jats:sub>\n                    , treatment with SSR182289 did not significantly decrease the area of fibrosis but significantly decreased the area of ASMA positive cells by 22% (p\u200a=\u200a0.03) and the expression of TIMP-1 mRNA by 52% (p\u200a=\u200a0.02). There was no effect on gene expression of collagen I, MMP-2, or TIMP-2. After seven weeks of CCl\n                    <jats:sub>4<\/jats:sub>\n                    , treatment with SSR182289 resulted in a significant decrease in fibrosis (\u221230%, p\u200a=\u200a0.04) and ASMA positive areas (\u221235%, p\u200a=\u200a0.05). SSR182289 alone had no effect on the measured parameters. Additionally, it did not alleviate the acute toxicity of CCl\n                    <jats:sub>4<\/jats:sub>\n                    as shown by measuring levels of serum aminotransferases and the area of necrosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    These data provide evidence that thrombin antagonism can reduce liver fibrogenesis. The early effect of SSR182289 on ASMA and TIMP-1 expression suggests that it is beneficial in reducing fibrogenic cell activation.\n                  <\/jats:p>","DOI":"10.1136\/gut.2003.032136","type":"journal-article","created":{"date-parts":[[2004,10,11]],"date-time":"2004-10-11T20:38:06Z","timestamp":1097527086000},"page":"1682-1687","source":"Crossref","is-referenced-by-count":67,"title":["A role for thrombin in liver fibrosis"],"prefix":"10.1136","volume":"53","author":[{"given":"J 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