Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs

Yanagita, Kimihiko; Nagaike, Mika; Ishibashi, Hiromi; Niho, Yoshiyuki; Matsumoto, Kunio; Nakamura, Toshikazu

doi:10.1016/0006-291x(92)91803-x

Cited by 200 publications

(97 citation statements)

References 18 publications

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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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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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“…The expression of c-met mRNA was strong hepatectomy or CCl 4 , and that nonparenchymal cells produce in the tissues of LEC rats with fulminant hepatitis and, HGF. [28][29][30][31][32][33] Both the levels of HGF mRNA and the activity of especially, in the cholangiofibrosis tissues. c-met mRNA HGF increase prior to liver regeneration.…”

Section: Cinoma (Hcc) Cells and The Cytoplasm Of The Nonepithe-mentioning

confidence: 99%

Hepatocyte growth factor and c-met expression in Long-Evans Cinnamon rats with spontaneous hepatitis and hepatoma

et al. 1996

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mal accumulation of copper in the liver of LEC rats, 40 times The Long-Evans Cinnamon (LEC) rat is characterized greater than that in control Long-Evans Agouti rats, whereas by the spontaneous onset of acute and chronic hepatitis, the levels of ceruloplasmin in LEC rat serum were markedly followed by occurrence of liver cancer, and is thus able low. [4][5] It is worth noting that these features of the liver disorto provide a unique experimental model for human geder in LEC rats are very similar to those that characterize netical liver disease, Wilson's disease. HepatocyteWilson's disease. [4][5][6][7] Recently, Wu et al. 8 cloned complemengrowth factor (HGF) is a potent hepatotrophic factor in tary DNAs for a rat gene (Atp7b) homologous to the human liver regeneration, and its expression is up-regulated inWilson's disease gene (ATP7B) and identified a partial deleresponse to liver injuries. We found that the plasma HGF tion in the Atp7b gene in the LEC rat. level in LEC rats rose markedly during the fulminant Hepatocyte growth factor (HGF) was first identified in the hepatitis phase, fell during the phase of chronic/cholanserum of partially hepatectomized rats 9 and purified from rat giofibrosis, and fluctuated during the hepatoma phase.platelets 10 and human plasma. 11,12 HGF is a ligand for the cImmunohistological staining of the liver revealed that met protooncogene product of receptor-type tyrosine kinase, 13-17 the number of HGF-positive cells increased remarkably and is considered to be a major hepatotrophic factor in the during the fulminant hepatitis phase, and that many of induction of mitosis of hepatocytes during liver regenerathese cells were localized at the portal triads. Fewer tion. [18][19][20] Acting as a motogen, HGF induces cell move-HGF-positive cells were observed during the phase of ment, 21,22 and, while acting as a morphogen, it induces the chronic hepatitis. The surface of the hepatocellular carformation of tissue-like structures [23][24][25] for various cell types. cinoma (HCC) cells and the cytoplasm of the nonepithe-The serum levels of HGF are elevated not only in human lial cells in cancerous liver tissues were HGF-positive.patients with fulminant hepatitis, but also in those with The HGF-messenger RNA (mRNA) level in the liver rose chronic hepatitis and cirrhosis. 26 HGF messenger RNA in the fulminant hepatitis phase, fell in the chronic hepa-(mRNA) is expressed in various tissues. 27 It has already been titis phase, and was intermediate or high during the hepreported that HGF production increases in rats injured by atoma phase. The expression of c-met mRNA was strong hepatectomy or CCl 4 , and that nonparenchymal cells produce in the tissues of LEC rats with fulminant hepatitis and, Both the levels of HGF mRNA and the activity of especially, in the cholangiofibrosis tissues. c-met mRNA HGF increase prior to liver regeneration. 28 It has also been was also detected in HCCs. These results suggest that reported that recombinant HGF has promoted remarkable the HGF-c-met system may pla...

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“…Previous studies have demonstrated that HGF has multifunctional activities such as mitogenic, morphogenic, and motogenic on a variety of epithelial cells (5,6), including pulmonary epithelial cells (7). Pulmonary mesenchymal cells synthesize and secrete HGF, which has been shown to be involved not only in the formation of bronchoalveolar structure during fetal development, but also in the repair process of injured distal organs such as liver and kidney (7)(8)(9)(10). In the bleomycin-induced lung injury model in rats (11), HGF showed the proliferative effect on type II alveolar epithelial cells, but showed the antiproliferative effect on alveolar macrophages and fibroblasts mainly implicated in the occurrence of fibrotic changes of the lung.…”

mentioning

confidence: 99%

Hepatocyte Growth Factor Protects Small Airway Epithelial Cells from Apoptosis Induced by Tumor Necrosis Factor-α or Oxidative Stress

et al. 2004

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Involvement of hepatocyte growth factor (HGF) in lung morphogenesis and regeneration has been established by in vitro and in vivo experiments in animals. In the present study, the protective activity of HGF against tumor necrosis factor (TNF)-␣ or hydrogen peroxide (H 2 O 2 )-induced damage of pulmonary epithelial cells was examined using the human small airway epithelial cell line (SAEC). Western blot analysis revealed that the receptor for HGF (c-Met) was highly expressed on the surface of SAEC and its downstream signal transduction pathway was functional. The SAEC was induced into apoptosis by the treatment with TNF-␣ or H 2 O 2 in a dose-dependant manner, but was significantly rescued from apoptosis in the presence of HGF. The HGF effect was evident when added not only at the same time but also within several hours after treatment. This protective activity of HGF against the TNF-␣-or H 2 O 2 -induced apoptosis was mediated, at least in part, by up-regulating the nuclear factor B activity and an increase in the ratio of apoptosis-suppressing to apoptosis-inducing proteins. These results suggest that administration of HGF might exhibit a potent function in vivo for protection and improvement of acute and chronic lung injuries induced by inflammation and/or oxidative stress. Lung development and morphogenesis begin in the fetal period of embryo and finally reach the formation of mature alveolar cells around 36 wk of gestation. The control of lung development is complicated and known to be influenced by the interaction between pulmonary epithelial and mesenchymal cells, which is mainly mediated by autocrine and paracrine mechanisms via a variety of polypeptides expressed on or secreted from mesenchymal cells (1).HGF, which was originally purified and cloned as a potent mitogen for mature hepatocytes in primary culture (2-4), is a cytokine mainly produced by cells of mesenchymal origin (5). Previous studies have demonstrated that HGF has multifunctional activities such as mitogenic, morphogenic, and motogenic on a variety of epithelial cells (5, 6), including pulmonary epithelial cells (7). Pulmonary mesenchymal cells synthesize and secrete HGF, which has been shown to be involved not only in the formation of bronchoalveolar structure during fetal development, but also in the repair process of injured distal organs such as liver and kidney (7-10). In the bleomycin-induced lung injury model in rats (11), HGF showed the proliferative effect on type II alveolar epithelial cells, but showed the antiproliferative effect on alveolar macrophages and fibroblasts mainly implicated in the occurrence of fibrotic changes of the lung. In addition, it has recently been shown that endogenous and exogenous HGF protects cardiac myocytes in a rat model of ischemia/reperfusion injury (12) and that the addition of HGF in the culture effectively protects adult rat cardiac myocytes from oxidative stress-induced apoptosis (13). Thus, it is speculated that HGF might play a role in the physiologic repair process of respiratory epithelium...

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Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs

Cited by 200 publications

References 18 publications

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

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

Hepatocyte growth factor and c-met expression in Long-Evans Cinnamon rats with spontaneous hepatitis and hepatoma

Hepatocyte Growth Factor Protects Small Airway Epithelial Cells from Apoptosis Induced by Tumor Necrosis Factor-α or Oxidative Stress

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