Abstract：
:We 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.
journal_name
Life Scijournal_title
Life sciencesauthors
Sakaida I,Hironaka K,Kimura T,Terai S,Yamasaki T,Okita Kdoi
10.1016/j.lfs.2003.09.059subject
Has Abstractpub_date
2004-03-19 00:00:00pages
2251-63issue
18eissn
0024-3205issn
1879-0631pii
S0024320503011688journal_volume
74pub_type
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