Changes in TIMP-1 and -2 expression in the early stage of porcine serum-induced liver fibrosis in rats.
It is widely recognized that tissue inhibitors of metalloproteinases (TIMPs), especially TIMP-1 and -2, play a key role in the progression of hepatic fibrosis. In the present study, we examined the changes in TIMP-1 and -2 expressions in the early stage of porcine serum (PS)-induced liver fibrosis in Brown Norway (BN) and Wistar rats. The rats were injected intraperitoneally with 0.5 ml/head of PS twice a week for up to 8 weeks and examined at 2, 4 and 8 weeks. Hepatic fibrosis and inflammatory cell infiltration developed at 4 and 8 weeks in BN and Wistar rats, respectively, and formation of pseudolobules was detected at 8 weeks in rats of both strains. The expression of liver TIMP-1 and -2 mRNAs significantly increased at 8 weeks in rats of both strains. At the same time, TIMP-1 and -2 activities were also detected in the liver of both strains. On the other hand, the expression of serum TIMP-1 and -2 proteins increased earlier (at 4 weeks for TIMP-1 and at 2 or 4 weeks for TIMP-2) than that of liver TIMP-1 and -2 mRNAs did. Although there are some reports suggestive of why the elevation of serum TIMP-1 and -2 proteins preceded that of liver TIMP-1 and -2 mRNAs, the exact reason is still obscure. In conclusion, the present study showed for the first time the mode of TIMP-1 and -2 expression and activity in the early stage of PS-induced rat liver fibrosis model.
Nippon Institute for Biological Science, 9-2221-1 Shin-machi, Ome, Tokyo 198-0024, Japan. y-baba@nibs.or.jp
Yasuko
Y
Hasegawa-Baba
Kunio
K
Doi
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum; D013552:Swine; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000096:biosynthesis*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000096:biosynthesis*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2