| Title | A role for thrombin in liver fibrosis |
| Publication Type | Journal Article |
| Year of Publication | 2004 |
| Authors | Duplantier JG, Dubuisson L, Senant N, Freyburger G, LAURENDEAU I, Herbert JM, Desmouliere A, Rosenbaum J |
| Journal | Gut |
| Volume | 53 |
| Issue | 11 |
| Pagination | 1682-7 |
| Abstract | {Background/ AIM: 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. METHODS: Fibrosis was induced in rats by administration of CCl(4) for either three or seven weeks. Oral administration of the thrombin antagonist SSR182289 started one week after the start of CCl(4) 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. RESULTS: After three weeks of CCl(4), treatment with SSR182289 did not significantly decrease the area of fibrosis but significantly decreased the area of ASMA positive cells by 22% (p = 0.03) and the expression of TIMP-1 mRNA by 52% (p = 0.02). There was no effect on gene expression of collagen I, MMP-2, or TIMP-2. After seven weeks of CCl(4), treatment with SSR182289 resulted in a significant decrease in fibrosis (-30% |
| URL | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15479692 |
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