C-myc and c-H-ras RNA expression in rat liver following intoxication with CC14

Milani, Stefano; Schuppan, Detlef; Herbst, H.; Surrenti, C.; Riecken, E. O.; Stein, Hans

doi:10.1016/0168-8278(89)90305-x

Cited by 14 publications

(19 citation statements)

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“…In liver injury of humans and experimental animals, lipocytes transform to a myofibroblast-like phenotype, proliferate, and are most abundant in regions of active fibrosis (2,3). By in situ hybridization, mRNA's for interstitial collagens are localized predominantly to activated lipocytes both in animal models ofliver fibrosis (4,5) and human liver disease (6). In culture, rat and human lipocytes synthesize interstitial collagens (7,8), laminin (9), fibronectin (10), and proteoglycans ( 11).…”

Section: Introductionmentioning

confidence: 99%

Human hepatic lipocytes synthesize tissue inhibitor of metalloproteinases-1. Implications for regulation of matrix degradation in liver.

Iredale¹,

Murphy²,

Hembry³

et al. 1992

J. Clin. Invest.

196

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Hepatic lipocytes play a central role in the pathogenesis of liver fibrosis, both via production of extracellular matrix proteins and through secretion of matrix metalloproteinases. In this study, we have characterized lipocyte expression and release of tissue inhibitor of metalloproteinases-1 (TIMP-1), an important inhibitor of metalloproteinase activity, whose role in liver has not previously been examined.TIMP-1 was immunolocalized to human lipocytes, and secretion of TIMP-1 was confirmed by ELISA of culture media; (mean±SD) 159±79 ng of TIMP-1/106 cells per 24 h. Evidence for functional inhibitory activity of released TIMP-1 was obtained by (a) reverse zymography that demonstrated a single inhibitor band, M, 28 kD, that co-migrated with a TIMP-1-positive control sample; and (b) unmasking of inhibited gelatinase activity in lipocyte medium by separating it from TIMP-1 using gelatin sepharose chromatography; gelatinase activity in chromatographed medium increased more than 20-fold, compared with unfractionated medium, and could be reinhibited by adding back fractions that contained inhibitor. By Northern analysis, freshly isolated human lipocytes exhibited low levels of mRNA expression for TIMP-1, but this increased markedly relative to #l-actin expression with lipocyte activation during cell culture.We conclude that human hepatic lipocytes synthesize TIMP-1, a potent metalloproteinase inhibitor, and that TIMP-1 expression increases with lipocyte activation. These data indicate that hepatic lipocytes can regulate matrix degradation in the liver, and suggest that expression of TIMP-1 by activated lipocytes may contribute to the progression of liver fibrosis. (J.

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Section: Introductionmentioning

confidence: 99%

Human hepatic lipocytes synthesize tissue inhibitor of metalloproteinases-1. Implications for regulation of matrix degradation in liver.

Iredale¹,

Murphy²,

Hembry³

et al. 1992

J. Clin. Invest.

196

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“…These cells are the major source ofcollagen production in the fibrotic liver (14)(15)(16). They are considered to play a pivotal role in the pathogenesis of liver fibrosis through a transition from a "quiescent" fat-storing phenotype to an "activated" myofibroblast-like appearance (17).…”

Section: Introductionmentioning

confidence: 99%

Cultured human liver fat-storing cells produce monocyte chemotactic protein-1. Regulation by proinflammatory cytokines.

Marra¹,

Valente²,

Pinzani³

et al. 1993

J. Clin. Invest.

192

128

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Monocytes infiltrate the portal space during chronic liver inflammation. Monocyte chemotactic protein-i (MCP-1) is a cytokine that induces monocyte chemotaxis and activation. We investigated if human liver fat-storing cells (FSC) secrete MCP-1, and the mechanisms that regulate MCP-1 production. Unstimulated FSC secrete MCP-1 as measured by radioimmunoassay as well as a chemotactic assay and express mRNA that encodes for this cytokine. A two-to threefold increase in MCP-1 secretion was observed when FSC were treated with either interleukin-la (IL-la) or interferon--y (IFN-"y). Tumor necrosis factor-a (TNFa) also increased MCP-1 secretion, although to a lesser extent (1.6-fold). Northern blot analysis showed that IL-la and IFN-'y strongly increase the levels of mRNA that encodes for MCP-1, whereas TNFa appears to be a weaker stimulus. Analysis of FSC-conditioned medium by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting revealed three bands of MCP-1 that most likely represent isoforms of different apparent molecular weights. Pretreatment of FSC with H-7, a protein kinase C inhibitor, blocked cytokine-induced increase in both MCP-1 gene expression and secretion. To determine the potential role of MCP-1 in vivo, we also analyzed normal and pathologic human liver tissue. Northern blot analysis showed that MCP-1 mRNA expression is more abundant in liver tissue obtained from patients with chronic active hepatitis compared with normal liver tissue. These studies indicate that MCP-1 secreted by FSC is stimulated by proinflammatory cytokines and that MCP-1 gene expression is upregulated in chronic inflammatory liver disease.

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“…Lipocytes, which remained at the top two interfaces, were collected and washed twice in culture medium followed by centrifugation at 500 g to remove hepatocyte debris. Endothelial cells, collected from the bottom two interfaces of the gradient, were purified further by centrifugal elutriation at 2,500 rpm and a flow rate of [10][11][12][13][14][15][16][17][18] Probe preparation. cDNAs encoding rat al(I) collagen (paIRI) (24), rat al(III) collagen (PRGR5) (Makela, J. K., and E. Vuorio, unpublished observations), mouse al(IV) collagen (pPE123) (25), and mouse laminin B2 chain (pPE9) (26) (27), which cross-hybridizes with rat fl-actin, was provided in SP64 by Dr. J. M. Friedman, The Rockefeller University, New York.…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo.

Maher¹,

McGuire²

1990

J. Clin. Invest.

410

271

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C-myc and c-H-ras RNA expression in rat liver following intoxication with CC14

Cited by 14 publications

References 0 publications

Human hepatic lipocytes synthesize tissue inhibitor of metalloproteinases-1. Implications for regulation of matrix degradation in liver.

Human hepatic lipocytes synthesize tissue inhibitor of metalloproteinases-1. Implications for regulation of matrix degradation in liver.

Cultured human liver fat-storing cells produce monocyte chemotactic protein-1. Regulation by proinflammatory cytokines.

Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo.

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