Prolyl 4-hydroxylase inhibitor (HOE 077) prevents TIMP-1 gene expression in rat liver fibrosis.

Abstract

The effects of a prolyl 4-hydroxylase inhibitor (HOE 077) on tissue inhibitor of metalloproteinase-1 (TIMP-1) and procollagen type I were examined in rat liver fibrosis. HOE 077 (200 ppm) prevented fibrosis by inhibiting the expression of liver type I procollagen and TIMP-1 mRNAs, with liver hydroxyroline content correlated with the reduction in activated stellate cells. HOE 077 prevents fibrosis by inhibiting proline hydroxylation and stellate cell activation, resulting in reduced expression of procollagen and TIMP-1 mRNAs.

• Authors: I Sakaida, K Uchida, K Hironaka, K Okita
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 34 Issue 3 Pg. 376-7 (Jun 1999) ISSN: 0944-1174 [Print] Japan
• PMID: 10433015 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Procollagen
• Pyridines
• Tissue Inhibitor of Metalloproteinase-1
• lufironil

Topics

• Animals
• Blotting, Northern
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Gene Expression (drug effects)
• Liver Cirrhosis, Experimental (genetics)
• Male
• Procollagen (genetics, metabolism)
• Pyridines (pharmacology)
• Rats
• Rats, Wistar
• Reference Values
• Tissue Inhibitor of Metalloproteinase-1 (drug effects, genetics)