Expression of hepatocyte growth factor gene in endothelial and kupffer cells of damaged rat livers, as revealed by insitu hydridization

Noji, Sumihara; Tashiro, Kosuke; Koyama, Eiki; Nohno, Tsutomu; Ohyama, Kazumi; Taniguchi, Shigehiko; Nakamura, Toshikazu

doi:10.1016/s0006-291x(05)81018-6

Cited by 281 publications

(121 citation statements)

References 12 publications

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“…We have not, however, investigated the source of EGF or HGF. HGF is produced by nonparenchymal cells, such as Kupffer cells, 35 sinusoidal endothelial cells 35 and hepatic stellate cells. 36 In addition, HGF is produced in other organs besides the liver, and so the sources of the serum HGF may be extrahepatic.…”

Section: Discussionmentioning

confidence: 99%

EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes

Barreiros

Sprinzl

Rosset

et al. 2008

Intl Journal of Cancer

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The hepatitis B virus (HBV) is a major causative agent of chronic liver disease and subsequent liver cirrhosis worldwide. The reduced sensitivity of virus-infected liver cells to apoptosis may play a role in the failure to remove virus-infected cells and eventually promote viral chronicity. The purpose of our study was to investigate whether survival factors induced during compensatory liver regeneration may protect hepatocytes against apoptosis. We evaluated the serum levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in HBV-infected patients and found significant increases in HGF and EGF in patients with active virus infection. In primary human hepatocytes we show that HGF and EGF have a protective effect against CD95-mediated apoptosis and cytotoxic T-cell killing. Simultaneous treatment with both regeneration factors enhanced the cytoprotective effect. The PI 3-K/Akt kinase inhibitor, wortmannin, and the STAT3 pathway inhibitor, Tyrphostin AG490, both effectively attenuated the cytoprotective effect of HGF and EGF. Furthermore, we show an EGF/HGF-dependent upregulation of b 1 -integrin chains, increased adhesion to extracellular matrix and an increase in focal adhesions, suggesting outside-in signaling from the extracellular matrix as an additional cytoprotective mechanism. Our study demonstrates that HGF and EGF can interfere with CD95-mediated apoptosis and the action of cytotoxic T-cells through multiple mechanisms in human hepatocytes. Together our results argue that a survival mileau generated by activation of liver regeneration factors may be a risk factor for establishing viral persistence.

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Section: Discussionmentioning

confidence: 99%

EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes

Barreiros

Sprinzl

Rosset

et al. 2008

Intl Journal of Cancer

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“…These consist of two chains linked together by disulphide bonds. Recent studies have suggested that HGF is produced by non-parenchymal hepatic cells including Kupffer cells (Noji et al, 1990), endothelial cells (Stoker et al, 1987;Shima et al, 1991), fibroblasts and fat-storing cells in the liver (Ramadori et al, 1992;Schirmacher et al, 1992), endothelial cells in the lung Yanagita et al, 1992). Experimentally, tumour cells are also known to produce HGF; HGF or mRNA encoding this factor has been detected in fibrosarcoma (Stoker et al, 1987), lung cancer (Yoshinaga et al, 1992;Rygaard et al, 1993;Tsao et al, 1993); hepatoma (Miyazaki et al, 1991) and pancreatic cancer cells (Hirota et al, 1993).…”

Section: Methodsmentioning

confidence: 99%

Serum hepatocyte growth factor as an index of disease status of patients with colorectal carcinoma

Fukuura

Miki²,

Inoue³

et al. 1998

Br J Cancer

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Summary To evaluate the clinical significance of serum levels of hepatocyte growth factor (HGF) in colorectal cancer patients, we measured the venous and portal concentrations of HGF in 60 patients. The tissue concentrations in the tumour and adjacent normal mucosa were also determined. The serum HGF concentration for the peripheral venous blood of the patients was significantly higher than that in normal controls. The content of HGF in cancer tissue was also significantly higher than that in normal mucosa, and it was correlated with the serum HGF concentration for the peripheral venous blood. The serum concentration of HGF reflected pathological features, including tumour size and lymph node or liver metastasis, and it showed an association with various preoperative nutritional parameters and the preoperative haemoglobin level. The serum HGF concentration was also correlated with the serum concentrations of immunosuppressive acidic protein and interleukin-6, indices of the host's immunological condition. Serum HGF seems to be a useful index of the disease status of patients with colorectal carcinoma.Keywords: hepatocyte growth factor; nutritional status; immunological status; colorectal cancer Hepatocyte growth factor (HGF) is a multifunctional cytokine that is the most potent known stimulator of hepatocyte growth and DNA synthesis Kaneko et al, 1992). HGF has also been recognized as a tumour-disseminating factor (Weidner et al, 1991;Mayer et al, 1993;Tannapfel et al, 1994). In several experimental studies, evidence has been acquired of a relation of HGF to the progression of tumour cells . Among the particularly important biological activities of HGF in tumour cells is its capacity to increase epithelial cell proliferation and motility (Gherardi et al, 1990). In clinical studies, a relationship between the concentration of HGF in serum or cancer tissue and the progression of disease has been noted in patients with gastric cancer (Taniguchi et al, 1997), oesophageal cancer (Takada et al, 1995) and breast cancer (Yamashita et al, 1994;Taniguchi et al, 1995). However, there are no reports regarding the clinical relevance of HGF in patients with colorectal carcinoma.Malnutrition or immunosuppression are involved in the development of life-threatening complications in patients with malignancies (Braga et al, 1988;Nishi et al, 1988;Dannhauser et al, 1995;Triantafillidis et al, 1995;Windsor et al, 1995;Goransson et al, 1996). Patients with advanced cancer and cachexia typically demonstrate modestly increased rates of energy expenditure with concomitant diminished food intake. These metabolic changes may be due to mediators released by the tumour or by the host (Keller, 1993). Recently, the role of cytokines in these metabolic changes was emphasized (Gambardella et al, 1997). In addition, the relationship between cytokines and an immunosuppressive substance has also been highlighted (Tanaka et al, 1993 The objective of this study was to evaluate the relationship between serum HGF concentration and clinicopathological ...

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“…It has also been found to be markedly increased in the livers of rats that suffered necrotic injury resulting from treatment with CC14 (38). After CC14 injury, there is a rapid rise in the level of HGF transcript in nonparenchymal cells (principally Kupffer cells), but not in hepatocytes (39). Further evidence of the role of HGF in liver regeneration has been provided by Higuchi et al (40), who recently identified a receptor on the surface of rat hepatocytes that binds HGF with high affinity.…”

Section: Proliferative Responses To Cytotoxic Damagementioning

confidence: 99%

Role of chemically induced cell proliferation in carcinogenesis and its use in health risk assessment.

Croy¹

1993

Environ Health Perspect

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There is much interest in incorporating knowledge of biological mechanisms of carcinogenesis into assessments of health risks to humans posed by chemicals in the environment. Debate over the soundness of using data from animal bioassays conducted at minimally toxic doses or fractions thereof for predicting cancer risks to humans exposed to much lower doses has stimulated interest in the question of whether genotoxic or mitotic effects predominate in chemical carcinogenesis. Cell division plays a key role at each stage in the evolution of cancer, and it is well documented that increased rates of cell proliferation can escalate the risk of malignancy. This article examines the current understanding of both mechanisms by which chemicals provoke cell proliferation and the contribution of various kinetic patterns of cell proliferation to carcinogenesis.

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Expression of hepatocyte growth factor gene in endothelial and kupffer cells of damaged rat livers, as revealed by insitu hydridization

Cited by 281 publications

References 12 publications

EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes

EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes

Serum hepatocyte growth factor as an index of disease status of patients with colorectal carcinoma

Role of chemically induced cell proliferation in carcinogenesis and its use in health risk assessment.

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