Stimulation of interstitial collagenase in co-cultures of rat hepatocytes and sinusoidal cells

Kazuo Kashiwazaki, Margaret S. Hibbs, Jerome M. Seyer, Carlo L. Mainardi, Andrew Kang

Research output: Contribution to journalArticle

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Abstract

Although the fibrosis observed during chronic liver injury is the result of a complex process, the striking accumulation of collagen in end stage liver disease has provoked interest in the mechanisms that regulate both collagen production and degradation in the diseased liver. The present studies have examined the cell interactions that may be important in the regulation of collagen degradation. Although minimal amounts of interstitial collagenase activity were noted in cultures of normal hepatocytes and sinusoidal cells, the co-cultures of these cells in the presence of lipopolysaccharide showed a substantial increase in collagenase activity. When the hepatocytes were obtained from rats that had been treated with carbon tetrachloride in vivo, the enhanced activity seen in the co-cultures did not require the addition of lipopolysaccharide. Further characterization of this interaction suggested that the increase in collagenolytic activity was partially due to the elaboration of soluble factors by the hepatocyte, which stimulated collagenase production by the sinusoidal cell population. Elaboration of collagenase activity by the sinusoidal cells was inhibited by cycloheximide, suggesting that protein synthesis was required. The proteolytic activity was abrogated by inhibitors of metalloproteinases but not by serine or thiol proteinase inhibitors. The degradation products of type I collagen were typical of the expected products seen with vertebrate collagenases. Thus, it appears that the increased collagenolytic activity detected in this co-culture system is attributable to the production of interstitial collagenase by the sinusoidal cell population. Such cell-cell interactions may play an important role in the maintenance of normal connective tissue structure of the liver during disease processes.

Original languageEnglish (US)
Pages (from-to)829-836
Number of pages8
JournalGastroenterology
Volume90
Issue number4
DOIs
StatePublished - Jan 1 1986

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Matrix Metalloproteinase 1
Coculture Techniques
Collagenases
Hepatocytes
Collagen
Cell Communication
Lipopolysaccharides
Liver Diseases
End Stage Liver Disease
Carbon Tetrachloride
Metalloproteases
Cycloheximide
Collagen Type I
Sulfhydryl Compounds
Connective Tissue
Serine
Population
Vertebrates
Fibrosis
Peptide Hydrolases

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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Stimulation of interstitial collagenase in co-cultures of rat hepatocytes and sinusoidal cells. / Kashiwazaki, Kazuo; Hibbs, Margaret S.; Seyer, Jerome M.; Mainardi, Carlo L.; Kang, Andrew.

In: Gastroenterology, Vol. 90, No. 4, 01.01.1986, p. 829-836.

Research output: Contribution to journalArticle

Kashiwazaki, Kazuo ; Hibbs, Margaret S. ; Seyer, Jerome M. ; Mainardi, Carlo L. ; Kang, Andrew. / Stimulation of interstitial collagenase in co-cultures of rat hepatocytes and sinusoidal cells. In: Gastroenterology. 1986 ; Vol. 90, No. 4. pp. 829-836.
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