Molecular mechanism of the reversibility of hepatic fibrosis

With special reference to the role of matrix metalloproteinases

Isao Okazaki, Tetsu Watanabe, Shigenari Hozawa, Masao Arai, Katsuya Maruyama

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

The participation of matrix metalloproteinases (MMP) and their specific inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMP), in both the formation and degradative recovery processes of liver fibrosis were mainly reviewed from the molecular biological aspect. Since authors first reported increased activity of interstitial collagenase in the early stage of hepatic fibrosis in rats induced by chronic CCl4 intoxication, in baboons fed alcohol chronically and in patients with alcoholic fibrosis, other investigators have also demonstrated increased activity biologically and histochemically. However, species-specific differences in response have been found and gene-level research on the rat model has not demonstrated increased mRNA transcription of collagenase. It has also been clarified that activated stellate cells can also produce matrix components. Very recently, authors observed the participation of interstitial collagenase in the recovery from experimental hepatic fibrosis by using polymerase chain reaction northern blotting and in situ hybridization. The in situ hybridization findings not only demonstrated the cells responsible for interstitial collagenase, but also suggested a great deal about the mechanism of recovery from fibrosis. Hepatic stellate cells are activated via the expression of c-myb and nuclear factor-κB (NFκB) which is induced by oxidative stress, and inhibited by antioxidant (1-α-tocopherol) and butylated hydroxytoluene. The activation mechanism is now being revealed. The relationship between the activation mechanism of stellate cells and the production and secretion of MMP and TIMP in the formation and recovery process of hepatic fibrosis should be investigated from the promoter gene level. This approach might help develop a new strategy for the treatment of liver fibrosis. (C) 2000 Blackwell Science Asia Pty Ltd.

Original languageEnglish
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume15
Issue numberSUPPL.
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Matrix Metalloproteinases
Fibrosis
Matrix Metalloproteinase 1
Liver
Tissue Inhibitor of Metalloproteinases
Liver Cirrhosis
In Situ Hybridization
Hepatic Stellate Cells
Butylated Hydroxytoluene
Matrix Metalloproteinase Inhibitors
Tocopherols
Papio
Collagenases
Northern Blotting
Genes
Oxidative Stress
Antioxidants
Alcohols
Research Personnel
Polymerase Chain Reaction

Keywords

  • Activation of stellate cell
  • Hepatic stellate cell
  • Matrix metalloproteinases
  • Myofibroblast
  • Promoter gene
  • Tissue inhibitors of matrix metalloproteinases

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Molecular mechanism of the reversibility of hepatic fibrosis : With special reference to the role of matrix metalloproteinases. / Okazaki, Isao; Watanabe, Tetsu; Hozawa, Shigenari; Arai, Masao; Maruyama, Katsuya.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 15, No. SUPPL., 2000.

Research output: Contribution to journalArticle

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