Changes in TIMP-1 and -2 expression in the early stage of porcine serum-induced liver fibrosis in rats.

Abstract

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.

• Authors: Yasuko Hasegawa-Baba, Kunio Doi
• Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie (Exp Toxicol Pathol) Vol. 63 Issue 4 Pg. 357-61 (May 2011) ISSN: 1618-1433 [Electronic] Germany
• PMID: 20226641 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier GmbH. All rights reserved.

Chemical References

• Tissue Inhibitor of Metalloproteinase-1
• Tissue Inhibitor of Metalloproteinase-2

Topics

• Animals
• Enzyme-Linked Immunosorbent Assay
• Gene Expression
• Liver Cirrhosis (chemically induced, enzymology, pathology)
• Male
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Serum
• Swine
• Tissue Inhibitor of Metalloproteinase-1 (analysis, biosynthesis)
• Tissue Inhibitor of Metalloproteinase-2 (analysis, biosynthesis)