TIMP EXPRESSION IN TOXIC AND CHOLESTATIC LIVER-INJURY IN RAT

Background/Aims: Hepatic fibrosis is a dynamic pathological process wi th a net accumulation of extracellular matrix proteins, Recent evidenc e suggests that besides their increased synthesis, inhibition of matri x degradation plays a significant role, ECM degradation occurs via met alloproteinases which are inhibited in situ by specific tissue inhibit ors of metalloproteinases (TIMPs), The aim of our studies was to deter mine 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 (in traperitoneal CCI4 injection and bile duct ligation) by Northern blot analysis and in situ hybridization. For comparison, the mRNA expressio n of the acute phase protein haptoglobin was measured. Results: TIMP-1 was increased during the early phase of toxic liver injury and in cho lestasis, Its expression occurred predominantly in areas of inflammati on, in hepatocytes, and in mesenchymal and endothelial cells, There wa s a slight upregulation of TIMP-2 expression during cholestasis. TIMP- 3 was not detected at all. Conclusions: Our results emphasize an invol vement of TIMP-1 in matrix homeostasis, indicating its possible partic ipation in liver fibrosis.