| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
NASH is a progressive fibrotic disease, which increasing the risk of developing hepatocellular carcinoma, however, there are still no efficient therapeutic strategy. In the present study, we examined efficacy of PRI-724 treatment to NASH-related liver fibrosis and characterized the mechanism of PRI-724 efficacy. By daily administering PRI-724 in NASH-induced liver fibrosis mice, normalization of hepatic architecture and decrease of collagen fibrils were observed after administration of PRI-724. Hepatic expressions of αSMA, type I and type III collagens, liver fibrosis markers, were significantly decreased. Moreover, expression of matrix metalloproteinase Mmp8 and Mmp9 in the liver were significantly increased. PRI-724 increased MMP-9 production in liver neutrophils and macrophages, therefore, MMP-9 is possibly contributing the improve of liver fibrosis. In conclusion, PRI-724, a selective Wnt/β-catenin/CBP inhibitor, shows therapeutic effect for NASH-related liver fibrosis/cirrhosis.
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