Expression of TIMP-1 and TIMP-2 in rats with hepatic fibrosis

World J Gastroenterol. 2004 Jan;10(1):86-90. doi: 10.3748/wjg.v10.i1.86.


Aim: To investigate the location and expression of TIMP-1 and TIMP-2 in the liver of normal and experimental hepatic fibrosis in rats.

Methods: The rat models of experimental immunity hepatic fibrosis (n=20) were prepared by the means of immunologic attacking with human serum albumin (HSA), and normal rats (n=10) served as control group. Both immunohistochemistry and in situ hybridization methods were respectively used to detect the TIMP-1 and TIMP-2 mRNA and related antigens in liver. The liver tissue was detected to find out the gene expression of TIMP-1 and TIMP-2 with RT-PCR.

Results: The TIMP-1 and TIMP-2 related antigens in livers of experimental group were expressed in myofibroblasts and fibroblasts (TIMP-1: 482+/-65 vs 60+/-20; TIMP-2: 336+/-48 vs 50+/-19, P<0.001). This was the most obvious in portal area and fibrous septum. The positive signals were located in cytoplasm, not in nucleus. Such distribution and location were confirmed by situ hybridization (TIMP-1/beta-actin: 1.86+/-0.47 vs 0.36+/-0.08; TIMP-2/beta-actin: 1.06+/-0.22 vs 0.36+/-0.08, P<0.001). The expression of TIMP-1 and TIMP-2 was seen in the liver of normal rats, but the expression level was very low. However, the expression of TIMP-1 and TIMP-2 in the liver of experimental group was obviously high.

Conclusion: In the process of hepatic fibrosis, fibroblasts and myofibroblasts are the major cells that express TIMPs. The more serious the hepatic fibrosis is in the injured liver, the higher the level of TIMP-1 and TIMP-2 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Fibroblasts / physiology
  • Gene Expression
  • Immunohistochemistry
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / physiopathology*
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Severity of Illness Index
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / genetics*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism


  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2