TIMP expression in toxic and cholestatic liver injury in rat

Background/Aims: Hepatic fibrosis is a dynamic pathological process with a net accumulation of extracellular matrix proteins. Recent evidence suggests that besides their increased synthesis, inhibition of matrix degradation plays a significant role. ECM degradation occurs via metalloproteinases which are inhibited in situ by specific tissue inhibitors of metalloproteinases (TIMPs). The aim of our studies was to determine the expression of TIMPs during toxic liver injury and cholestatic liver injury leading to fibrosis. Methods: We examined the expression of TIMP-1, -2 and -3 in two different rat models for liver injury (intraperitoneal CCl4 injection and bile duct ligation) by Northern blot analysis and situ hybridization. For comparison, the mRNA expression of the acute phase protein haptoglobin was measured. Results: TIMP-1 was increased during the early phase of toxic liver injury and in cholestasis. Its expression occurred predominantly in areas of inflammation, in hepatocytes, and in mesenchymal and endothelial cells. There was a slight upregulation of TIMP-2 expression during cholestasis. TIMP-3 was not detected at all. Conclusions: Our results emphasize an involvement of TIMP-1 in matrix homestasis, indicating its possible participation in liver fibrosis.