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SB203580 diminished the reduction of mRNA as well as the activity of TIMP-1 by TJ-9 and induction of mRNA as well as the activity of MMP-2. These results show that TJ-9 increased MMP-2, 13 activity with reduced TIMP-1, 2 activities on HSCs possibly via P38 pathway."}

{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":185},"obj":"DRI_Background"},{"id":"T2","span":{"begin":186,"end":260},"obj":"DRI_Approach"},{"id":"T3","span":{"begin":261,"end":417},"obj":"DRI_Approach"},{"id":"T4","span":{"begin":418,"end":564},"obj":"DRI_Background"},{"id":"T5","span":{"begin":565,"end":746},"obj":"DRI_Approach"},{"id":"T6","span":{"begin":747,"end":842},"obj":"DRI_Approach"},{"id":"T7","span":{"begin":843,"end":970},"obj":"DRI_Background"},{"id":"T8","span":{"begin":971,"end":1182},"obj":"DRI_Background"},{"id":"T9","span":{"begin":1183,"end":1322},"obj":"DRI_Outcome"},{"id":"T10","span":{"begin":1323,"end":1448},"obj":"DRI_Background"}],"text":"Herbal medicine Sho-saiko-to (TJ-9) increases expression matrix metalloproteinases (MMPs) with reduced expression of tissue inhibitor of metalloproteinases (TIMPs) in rat stellate cell.\nWe have reported that Sho-saiko-to (TJ-9) prevents liver fibrosis in vivo. To gain further insights into the effect of TJ-9, the matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) balance was examined. Hepatic stellate cells (HSCs) were isolated from male Wistar rats and cultured with TJ-9 (0-1000 microg/ml) on uncoated plastic dishes for 4 days. To elucidate the effects on the MMPs/TIMPs balance by TJ-9, quantitative analysis of type IV collagen-degrading activity, gelatin zymography and reverse zymography were carried out. Northern blot analysis was performed to determine the expression of MMP-2, 13 and TIMP-1 mRNAs. TJ-9 treatment resulted in dose-dependent upregulation of MMP-2, 13 mRNA and downregulation of TIMP-1 mRNA up to 500 microg/ml. Gelatin zymography, reverse zymography and quantitative analysis of type IV collagen-degrading activity confirmed that TJ-9 increased MMP-2 activity and prevented TIMP-1, 2 activities in a dose-dependent manner. SB203580 diminished the reduction of mRNA as well as the activity of TIMP-1 by TJ-9 and induction of mRNA as well as the activity of MMP-2. These results show that TJ-9 increased MMP-2, 13 activity with reduced TIMP-1, 2 activities on HSCs possibly via P38 pathway."}

{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":186,"end":260},"obj":"DRI_Approach"},{"id":"T2","span":{"begin":261,"end":417},"obj":"DRI_Approach"},{"id":"T3","span":{"begin":418,"end":564},"obj":"DRI_Background"},{"id":"T4","span":{"begin":565,"end":746},"obj":"DRI_Approach"},{"id":"T5","span":{"begin":747,"end":842},"obj":"DRI_Approach"},{"id":"T6","span":{"begin":843,"end":970},"obj":"DRI_Background"},{"id":"T7","span":{"begin":971,"end":1182},"obj":"DRI_Background"},{"id":"T8","span":{"begin":1183,"end":1322},"obj":"DRI_Outcome"},{"id":"T9","span":{"begin":1323,"end":1448},"obj":"DRI_Background"}],"text":"Herbal medicine Sho-saiko-to (TJ-9) increases expression matrix metalloproteinases (MMPs) with reduced expression of tissue inhibitor of metalloproteinases (TIMPs) in rat stellate cell.\nWe have reported that Sho-saiko-to (TJ-9) prevents liver fibrosis in vivo. To gain further insights into the effect of TJ-9, the matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) balance was examined. Hepatic stellate cells (HSCs) were isolated from male Wistar rats and cultured with TJ-9 (0-1000 microg/ml) on uncoated plastic dishes for 4 days. To elucidate the effects on the MMPs/TIMPs balance by TJ-9, quantitative analysis of type IV collagen-degrading activity, gelatin zymography and reverse zymography were carried out. Northern blot analysis was performed to determine the expression of MMP-2, 13 and TIMP-1 mRNAs. TJ-9 treatment resulted in dose-dependent upregulation of MMP-2, 13 mRNA and downregulation of TIMP-1 mRNA up to 500 microg/ml. Gelatin zymography, reverse zymography and quantitative analysis of type IV collagen-degrading activity confirmed that TJ-9 increased MMP-2 activity and prevented TIMP-1, 2 activities in a dose-dependent manner. SB203580 diminished the reduction of mRNA as well as the activity of TIMP-1 by TJ-9 and induction of mRNA as well as the activity of MMP-2. These results show that TJ-9 increased MMP-2, 13 activity with reduced TIMP-1, 2 activities on HSCs possibly via P38 pathway."}