Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased levels of expression of hepatocyte growth factor (HGF) and its specific receptor c-met have been shown in the liver of several benign and malignant pathologies, both in experimental models and humans. We investigated by immunohistochemistry the presence of both HGF and c-met protoocogene product (c-met pp) in 20 hepatocellular carcinomas (HCCs), 5 focal nodular hyperplasias (FNHs), 4 cases of fulminant hepatitis (FH), and 1 case of regenerated liver. The c-met protooncogene product was expressed in all cases with marked overexpression in the HCCs and in ductular metaplasia. HGF was detected in the Ito cells of all cases and in neoplastic hepatocytes of 9 of 20 HCCs (45%). The proliferative index of each lesion was evaluated by means of the polyclonal antibody anti-cyclin A. When the level of expression of HGF and c-met protooncogene product with the percentage of cyclin A+ nuclei were compared, the closest relationship was between c-met protooncogene product and cyclin A+ nuclei were compared, the closest relationship was between c-met protooncogene product and cyclin A. In 11 of 20 HCCs (55%), there wa no correlation between HGF positivity and cyclin A. This seems to suggest that, independently of the levels of native liver HGF, c-met protooncogene product is the most active modulator of liver cell proliferation.
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PMID:Liver hepatocyte growth factor does not always correlate with hepatocellular proliferation in human liver lesions: its specific receptor c-met does. 870 84

The Long-Evans Cinnamon (LEC) rat is characterized by the spontaneous onset of acute and chronic hepatitis, followed by occurrence of liver cancer, and is thus able to provide a unique experimental model for human genetical liver disease, Wilson's disease. Hepatocyte growth factor (HGF) is a potent hepatotrophic factor in liver regeneration, and its expression is up-regulated in response to liver injuries. We found that the plasma HGF level in LEC rats rose markedly during the fulminant hepatitis phase, fell during the phase of chronic/cholangiofibrosis, and fluctuated during the hepatoma phase. Immunohistological staining of the liver revealed that the number of HGF-positive cells increased remarkably during the fulminant hepatitis phase, and that many of these cells were localized at the portal triads. Fewer HGF-positive cells were observed during the phase of chronic hepatitis. The surface of the hepatocellular carcinoma (HCC) cells and the cytoplasm of the nonepithelial cells in cancerous liver tissues were HGF-positive. The HGF-messenger RNA (mRNA) level in the liver rose in the fulminant hepatitis phase, fell in the chronic hepatitis phase, and was intermediate or high during the hepatoma phase. The expression of c-met mRNA was strong in the tissues of LEC rats with fulminant hepatitis and, especially, in the cholangiofibrosis tissues. c-met mRNA was also detected in HCCs. These results suggest that the HGF-c-met system may play an important role in the regeneration of hepatocytes as well as in the development of HCC in paracrine or autocrine mechanisms.
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PMID:Hepatocyte growth factor and c-met expression in Long-Evans Cinnamon rats with spontaneous hepatitis and hepatoma. 878 31

Endothelial cells are known to secrete various antiproliferative and vasodilating factors, such as nitric oxide and natriuretic peptides. The presence of endothelial dysfunction, well known in hypertensive individuals, potentially results in the development and progression of atherosclerosis. Therefore, it is important to know the factors that might influence endothelial cell growth. We examined the mitogenic actions of hepatocyte growth factor (HGF) on human endothelial and vascular smooth muscle cells. Exogenously added human recombinant HGF stimulated endothelial but not vascular smooth muscle cell growth in a dose-dependent manner. We also compared the mitogenic action of HGF with that of basic fibroblast growth factor and vascular endothelial growth factor. Interestingly, the mitogenic action of HGF on endothelial cells was greater than the actions of basic fibroblast growth factor and vascular endothelial growth factor, whereas basic fibroblast growth factor but not HGF and vascular endothelial growth factor stimulated vascular smooth muscle cell growth. Given the characteristics of HGF as an endothelium-specific growth factor, we evaluated the relationship of circulating HGF and blood pressure in normotensive and hypertensive subjects. Serum HGF concentration has been reported to be elevated in response to organ damage, such as in hepatitis and nephritis, and recent findings show that HGF may play an important role in tissue regeneration. We hypothesized that HGF might contribute to the protection or repair of vascular endothelial cells. If so, serum HGF level might be elevated in response to endothelial cell damage induced by hypertension. To test this hypothesis, we measured serum levels of HGF, lipoprotein(a), plasminogen activator inhibitor-1, tissue plasminogen activator, total cholesterol, and blood pressure in 41 normotensive and hypertensive subjects without liver, kidney, or lung damage. Serum HGF concentration was significantly correlated with systolic pressure (P < .01, r = .43) but not diastolic pressure. Serum HGF concentration in hypertensive subjects was significantly higher than in normotensive subjects. None of the other factors showed any correlation with blood pressure. We have demonstrated that HGF is an endothelium-specific growth factor whose serum concentration is significantly associated with systolic pressure. These results suggest that HGF secretion might be elevated in response to high blood pressure as a counterregulatory system against endothelial dysfunction.
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PMID:A vascular modulator, hepatocyte growth factor, is associated with systolic pressure. 879 25

We studied the relationship of serum levels of human hepatocyte growth factor (hHGF) to causative viruses and clinical features in 63 patients at our hospital with serologically diagnosed acute viral hepatitis. Serum levels of hHGF were not correlated with the type of hepatitis virus (A, B, and C) during the acute phase (p < 0.60) but were correlated with results of the hepaplastin test (p < 0.01). Furthermore, the difference in serum levels of hHGF between severe (levels on hepaplastin test < 40%) and nonsevere cases of hepatitis was significant (p < 0.001), and serum levels of hHGF became normal as levels of alanine aminotransferase decreased. However, serum levels of hHGF in prolonged cases of hepatitis (time until normalization of alanine aminotransferase > 13 weeks) tended to be slightly lower than in nonprolonged cases (p < 0.47). These results suggest that serum levels of hHGF are useful to determine the prognoses of patients with severe hepatitis and to estimate the time until liver damage heals.
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PMID:[Clinical significance of serum levels of human hepatocyte growth factor in patients with acute viral hepatitis]. 880 50

The hepatocyte growth factor (HGF) regulates growth, motility, and morphogenesis of epithelial and endothelial cells. It has been reported that serum level of HGF was elevated in patients with having fulminant hepatitis. In inflammatory myopathies (IM), muscle cells are damaged by the inflammatory process and subsequently regenerated. HGF may be involved in the regeneration process of muscle cells in IM. We examined serum HGF was measured by ELISA from 13 patients with having polymyositis (PM), 18 patients with having dermatomyositis (DM), 3 patients with amyopathic dermatomyositis (ADM) and 14 normal individuals. The muscle of IM patients was examined by immunofluorescence staining using a monoclonal anti-HGF antibody. The serum HGF level was significantly higher in IM patients (0.63 +/- 0.11 (p = 0.028) in PM, 0.58 +/- 0.07 (p = 0.023) in DM) than in normal controls (0.26 +/- 0.01 ng/ml). However, there was no relationship between the serum HGF level and hepatic enzyme level in IM. The levels of serum HGF were significantly higher in active disease (1.05 +/- 0.26 ng/ml) than in inactive disease (0.29 +/- 0.03 ng/ml) (p = 0.044). The serum HGF levels (0.77 +/- 0.12 ng/ ml) were significantly higher in IM patients with pulmonary fibrosis than in those (0.42 +/- 0.04 ng/ml) without pulmonary fibrosis (p = 0.049). There was a positive relationship between serum HGF levels and the presence of opaque fiber and/or regeneration/degeneration fiber in biopsied muscles. HGF was detected in muscles from IM patients by immunofluorescence. Serum HGF levels are elevated in IM and correlated with disease activity and complication of interstitial pneumonia.
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PMID:[Serum hepatocyte growth factor (HGF) in patients with inflammatory myopathies]. 895 17

Hepatocyte growth factor (HGF) has been reported to be a potent mitogen for hepatocytes in vivo and in vitro. Recent reports have shown that HGF has cytoprotective actions in acute liver injury models, but its mechanisms remain to be resolved. In the present study, we investigated whether HGF could work as an anti-hepatitis agent for acute liver injury caused by D-galactosamine (D-GalN) using transgenic (TG) mice expressing HGF in hepatocytes, compared with wild-type (WT) mice of their siblings. After administration of 3 g/kg body weight of D-GalN, elevated serum transaminase levels and severe liver damage that were observed in WT mice were significantly improved in TG mice. In TG mice, the percentage of proliferating cell nuclear antigen (PCNA)-positive hepatocytes was high at 0 hours after D-GalN treatment, and increased at 24 hours. The percentage of PCNA-positive cells in WT mice was very low at 0 hours and 24 hours after treatment, but increased at 48 hours. To clarify the mechanisms via which HGF acts, we measured hepatic HGF and prostaglandin E2 (PGE2) contents after D-GalN administration by an enzyme immunoassay. Total hepatic HGF contents, which were composed of murine (endogeneous) and human (derived from transgene) HGF, in TG mice were higher than those in WT mice at 0, 12, and 24 hours after administration of 3 g/kg body weight of D-GalN. Hepatic PGE2 contents in TG mice were also significantly higher than those in WT mice. Hepatic PGE2 contents had a positive correlation with total HGF contents at both 12 hours and 24 hours after the treatment. Moreover, an administration of 0.5 microg of anti-HGF antibody into the portal vein suppressed hepatic PGE2 contents of mice, compared with saline-injected mice in acute liver injury. Anti-PGE2 antibody administration caused more severe liver damage than saline solution. A survival rate of TG mice that were given 6 g/kg body weight of D-GalN-a lethal dose of D-GalN-was improved compared with WT mice. These results provided direct evidences that HGF worked as an anti-hepatitis agent against acute liver injury caused by D-GalN, and that this action might be exerted through accelerated hepatic PGE2 production.
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PMID:Protective action of hepatocyte growth factor for acute liver injury caused by D-galactosamine in transgenic mice. 936 68

The Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis in Fas-expressing cells. A matrix metalloproteinase-like enzyme cleaves the membrane-bound FasL to produce the soluble FasL (sFasL). Since FasL has been reported to play a pivotal role in the development of hepatitis, we evaluated clinical significance of serum sFasL in acute liver injury including acute self-limited and fulminant hepatitis. Serum sFasL in 19 patients including 12 with acute self-limited hepatitis and 7 with fulminant hepatitis was measured by an enzyme-linked immunosorbent assay (ELISA). The clinical data consisted of 18 indices including age, sex, liver function tests, hepatocyte growth factor (HGF), outcome and sFasL. Serum sFasL in fulminant hepatitis is 0.06+/-0.01 ng/ml, being identical to that in acute self-limited hepatitis, Serum sFasL is positively correlated with AST and ALT (p<0.0001 and p<0.0001). The factors associated with outcome of the patients were HGF, albumin, prothrombin time, platelet count, cholinesterase and leukocyte count in this order. Serum sFasL serves as an indicator of liver injury in acute self-limited and fulminant hepatitis.
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PMID:Clinical significance of serum soluble Fas ligand in patients with acute self-limited and fulminant hepatitis. 975 39

To examine the effect of nongenotoxic chemicals on hepatocarcinogenesis in Long-Evans Cinnamon (LEC) rats, we gave 6-week-old male and female LEC rats (n = 18) weekly subcutaneous injections of D-galactosamine hydrochloride (GalN, 300 mg/kg) in 0.9% NaCl or only 0.9% NaCl for 50 weeks, and killed them in week 62. GalN-treated male rats unexpectedly showed no lethal necrotizing hepatitis. GalN treatment increased the incidence of cholangiofibrosis in males and its severity in females, but did not cause significant increases of hepatocellular tumors in either sex. GaIN treatment increased the 5-bromo-2'-deoxyuridine (BrdU)-labeling index of hepatocytes and plasma hepatocyte growth factor, and accelerated megalocytic alterations without reduction of the hepatic copper concentration. Next, male and female LEC rats were subjected to two-thirds partial hepatectomy (PH) or sham hepatectomy in week 8 (n = 12) or in week 14 (n = 9), and killed in week 62. PH in week 14 inhibited lethal hepatitis, but PH in week 8 was less effective. PH reduced the hepatic copper concentration to half that of controls. The present data suggest that induction of hepatocyte regeneration by repeated injections of GalN, or by PH just before the onset of jaundice has a significant effect in prevention of hepatic injury of LEC rats, but not enhancement of spontaneous hepatocarcinogenesis.
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PMID:Effects of D-galactosamine hydrochloride and partial hepatectomy on spontaneous hepatic injury and hepatocarcinogenesis in Long-Evans Cinnamon rats. 1039 Oct 88

Hepatocyte growth factor/scatter factor (HGF/SF) is one of the most important humoral mediators of liver regeneration. It is potentially related to molecular mechanisms of hepatocarcinogenesis via a paracrine system involving its cellular receptor, c-met. In this study, the expression patterns of HGF and c-met were evidenced by multiplex RT-PCR in different specimens of human hepatic tissues (n = 71). A significant increase of c-met mRNA expression was detected in hepatitis (P = 0.001), cirrhosis (P = 0.006), and hepatocellular carcinoma (HCC) tissue (P = 0.003) compared with normal parenchyma and steatosis. HGF mRNA expression was significantly higher only in hepatitis (P = 0.01). Over-expression of c-met mRNA and under-expression of HGF mRNA were detected in the HCCs compared with the corresponding peri-tumoral tissues. Neither HGF nor c-met expression was related to age, sex, tumor size, grading, presence of pseudocapsula, and proliferative activity of the malignant hepatocytes. A significant inverse correlation was found between c-met mRNA expression level and survival (in months) of patients (P = 0.007), as previously shown for urokinase-type plasminogen activator (u-PA) mRNA (P = 0.027). In addition, c-met mRNA expression was strictly associated with u-PA mRNA level in HCC samples (P = 0.001). These data show that a loss of balance concerning HGF, c-met, and u-PA mRNA expression occurs during hepatocarcinogenesis. Particularly, up-regulation of c-met and u-PA mRNA transcription appears to be coordinately regulated, and their levels of expression are inversely correlated with survival; they must therefore play an important role in the development and progression of human HCC and may also be relevant prognostic markers.
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PMID:u-PA and c-MET mRNA expression is co-ordinately enhanced while hepatocyte growth factor mRNA is down-regulated in human hepatocellular carcinoma. 1092 56

Nephromegaly, assessed by calculating kidney volume using renal ultrasound, was studied in infants with biliary atresia, neonatal hepatitis, or fulminant hepatitis. We evaluated kidney volume in 29 patients with biliary atresia, 17 patients with neonatal hepatitis, and 10 patients with fulminant hepatitis, as well as 32 healthy infants. Levels of plasma hepatocyte growth factor (HGF) were measured in all infants. Levels of plasma transforming growth factor-beta1 (TGF-beta1) were also measured in diseased infants and 20 healthy infants. Significant nephromegaly was found in infants with biliary atresia compared with healthy infants (P < 0.001 by analysis of covariance). Marked nephromegaly was also noted in all infants with fulminant hepatitis and 35% of infants with neonatal hepatitis. No nephromegaly was found in infants at 2 months of age with biliary atresia or neonatal hepatitis despite mildly elevated plasma HGF levels. Regardless of the duration of HGF exposure and healthy renal growth by a certain age, a positive correlation existed between plasma HGF level and kidney volume (r = 0.529; P < 0.001), but an inverse correlation was found between plasma TGF-beta1 level and nephromegaly (r = -0.505; P < 0.001) in all diseased infants. There was a stronger positive correlation between plasma HGF-TGF-beta1 ratio and kidney volume (r = 0.666; P < 0.001) and degree of nephromegaly (r = 0.717; P < 0.001). These results confirm the presence of large kidneys not only in patients with biliary atresia but also in patients with fulminant hepatitis, which suggests the possible pathogenic role of HGF and manifests as elevated HGF-TGF-beta1 ratios in patients with such conditions. Nephromegaly in patients with severe or chronic liver dysfunction may provide a new in vivo model to study the mechanisms of renal growth.
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PMID:Nephromegaly and elevated plasma hepatocyte growth factor-transforming growth factor-beta1 ratio in infants with fulminant hepatitis or biliary atresia. 1147 53


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