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

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2011-05, Vol.63 (4), p.357-361
• Main Authors: Hasegawa-Baba, Yasuko, Doi, Kunio
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Enzyme-Linked Immunosorbent Assay; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Investigative techniques, diagnostic techniques (general aspects); Liver Cirrhosis - chemically induced; Liver Cirrhosis - enzymology; Liver Cirrhosis - pathology; Liver fibrosis; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Other diseases. Semiology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Porcine serum; Rat; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Serum; Swine; TIMP-1; TIMP-2; Tissue Inhibitor of Metalloproteinase-1 - analysis; Tissue Inhibitor of Metalloproteinase-1 - biosynthesis; Tissue Inhibitor of Metalloproteinase-2 - analysis; Tissue Inhibitor of Metalloproteinase-2 - biosynthesis
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2010.02.011

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.