Identification and characterization of "injurin," an inducer of expression of the gene for hepatocyte growth factor.

Matsumoto, Kunio; Tajima, Hiromi; Hamanoue, Masahiro; Kohno, Seiho; Kinoshita, Taisei; Nakamura, Toshikazu

doi:10.1073/pnas.89.9.3800

Cited by 140 publications

(60 citation statements)

References 37 publications

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“…In this regard, we found in the present study that the level of REG IV expression showed significant positive correlations with those of bFGF and HGF, although the REG IV gene is expressed in colonic epithelial cells while bFGF and HGF are produced mainly by interstitial mesenchymal cells. [23][24][25][26] These findings may indicate the presence of mutual interaction between growth factors in the epithelium and those in the interstitial cells.…”

Section: Effects Of Reg IVmentioning

confidence: 88%

Expression of the REG IV gene in ulcerative colitis

Nanakin

Fukui

Fujii

et al. 2007

Laboratory Investigation

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The regenerating gene (REG) IV gene was isolated from a cDNA library of ulcerative colitis (UC) tissues. However, its role in the pathophysiology of UC and subsequent development of colitic cancer is still unclear. We investigated the expression of the REG IV gene in UC and colitic cancer tissues and examined whether cytokines or growth factors are responsible for REG IV gene expression and whether REG IV gene induction affects cell growth and apoptosis in colon cancer cells. The expressions of REG IV and growth factor genes in UC tissues were analyzed by real time reverse transcription-polymerase chain reaction. The effects of cytokines and growth factors on REG IV gene expression were examined in SW403 cells by Northern blot analysis. The effects of REG IV gene induction on cell growth and H 2 O 2 -induced apoptosis were examined in DLD-1 cells by MTT and TUNEL assays, respectively. REG IV mRNA was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG IV mRNA expression was correlated with that of basic fibroblast growth factor (bFGF) as well as hepatocyte growth factor (HGF) mRNA expression in UC tissues. The REG IV gene expression in SW403 colon cancer cells was enhanced by stimulation with transforming growth factor-a, epidermal growth factor, bFGF, and HGF. REG IV gene induction promoted cell growth and conferred resistance to H 2 O 2 -induced apoptosis in DLD-1 cells. The REG IV gene is inducible by growth factors and may function as a growth promoting and/or an antiapoptotic factor in the pathophysiology of UC. The pathogenesis of ulcerative colitis (UC) is still unclear, but dysregulated immune function appears to be involved in its chronic inflammatory process, resulting in continuous damage of the colonic mucosa. [1][2][3][4][5] To regenerate the injured colonic tissues, growth factors are thought to play very important roles, and indeed, several growth factors are reported to be upregulated in the colonic tissues in UC. 3,6,7 However, few comprehensive studies have examined the expression patterns of various growth factors in UC tissues simultaneously, and the network of and the relationships among growth factors in UC tissues are not fully understood.Regenerating gene (REG) IV, the most recently discovered member of the REG gene family, was isolated from a cDNA library of UC tissues by Hartupee et al. 8 Although the biological function of REG IV protein is still unclear, REG IV protein may play a role in cell growth because other REG family proteins have been shown to act as growth factors in gastrointestinal organs. 9-14 However, it still remains unknown whether the REG IV gene is indeed involved in the pathophysiology of UC and whether REG IV protein really functions as a growth factor. Moreover, it has not been examined how REG IV gene expression is regulated. In the present study, therefore, in order to elucidate roles for REG IV in the pathophysiology of UC, we investigated the relationship between REG IV gene expression and clinicopat...

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Section: Effects Of Reg IVmentioning

confidence: 88%

Expression of the REG IV gene in ulcerative colitis

Nanakin

Fukui

Fujii

et al. 2007

Laboratory Investigation

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“…It is regulated during development (DeFrances et al, 1992;Sonnenberg et al, 1993), and by hormones and cytokines (Matsumoto et al, 1992a, b;Moghul et al, 1994;Tamura et al, 1993) in a variety of tissues under physiological and pathological conditions. Among the regulatory molecules, injurin, which is produced by injured organs, is known to influence HGF/ SF gene expression (Matsumoto et al, 1992a). One Mars et al, 1993;Miyazawa et al, 1993;Shimomura et al, 1995); these are serum proteases, such as blood coagulation factor XIIa and its homologous protein named HGF-activator, and the urokinase-type plasminogen activator (uPA).…”

Section: Discussionmentioning

confidence: 99%

Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas

Olivero¹,

et al. 1996

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Summary Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasive growth of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both the receptor and the ligand are detected, and the latter is known to be a mitogenic and a motogenic factor for both cultured bronchial epithelial cells and non-small-cell carcinoma lines. Here, ligand and receptor expression was examined in 42 samples of primary human non-small-cell lung carcinoma of different histotype. Each carcinoma sample was compared with adjacent normal lung tissue. The MetlHGF receptor was found to be 2 to 10-fold increased in 25% of carcinoma samples (P=0.0113). The ligand, HGF/SF, was found to be 10 to 100-fold overexpressed in carcinoma samples (P<0.0001). Notably, while HGF/SF was occasionally detectable and found exclusively as a single-chain inactive precursor in normal tissues, it was constantly in the biologically-active heterodimeric form in carcinomas. Immunohistochemical staining showed homogeneous expression of both the receptor and the ligand in carcinoma samples, whereas staining was barely detectable in their normal counterparts. These data show that HGF/SF is overexpressed and consistently activated in non-small-cell lung carcinomas and may contribute to the invasive growth of lung cancer.

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“…This suggests that expression of HGF and HGF receptor is regulated by different mechanisms. Considering the regulation of H G F expression, we recently found that injurin, a humoral factor which induces HGF-gene expression, appears to be involved in the induction of HGF following various organ injuries [46]. Kamalati et al found that HGF mRNA in MRC-5 human embryonic lung fibroblasts is strongly suppressed under heterotypic co-culture with several types of epithelial cells [47].…”

Section: Discussionmentioning

confidence: 99%

Developmental changes in hepatocyte growth factor mRNA and its receptor in rat liver, kidney and lung

Kagoshima

Kinoshita

Matsumoto

et al. 1992

European Journal of Biochemistry

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Hepatocyte growth factor (HGF) is a mesenchymal‐derived factor which induces mitosis, cell movement and morphogenesis of tissue‐like structure. We analyzed changes in HGF mRNA and its receptor, the c‐met proto‐oncogene product, in the liver, kidney and lung during late fetal and postnatal development in rats. In the liver, the HGF‐mRNA level was very low during late gestation and in neonates, it increased remarkably and reached a maximum two weeks postnatally, to be followed by a decrease to 33% of the maximum. HGF mRNA in the kidney and lung was either undetectable or very low during late gestation and the neonatal period and increased markedly to reach a maximum, respectively, 3–4 weeks postnatally. HGF‐mRNA level in the adult rat lung was fivefold higher than that in the liver and kidney. The number of HGF receptors on plasma membranes of these tissues was low in neonates but there was a rapid increase after birth and a maximum was reached within three weeks. The number of HGF receptors/ng plasma membrane protein at the maximal level was highest in the liver and lowest in the lung. c‐met/HGF‐receptor mRNA in the liver was also low during late‐gestation or in early neonatal periods and increased postnatally. Since HGF‐mRNA and HCF‐receptor levels changed differently in liver, kidney and lung, the expression of HGF and its receptor may be independently regulated in each organ. However, in these organs, HGF mRNA and the HGF receptor increased within a few weeks of birth, HGF may play roles in organ growth, organ maturation and the maintenance of tissue homeostasis during the postnatal period, presumably through its potential to act as mitogen, motogen and morphogen.

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Identification and characterization of "injurin," an inducer of expression of the gene for hepatocyte growth factor.

Abstract: The marked and rapid increase of hepatocyte growth factor (HGF) mRNA in the intact lung of rats after partial hepatectomy or unilateral nephrectomy suggests

Cited by 140 publications

References 37 publications

Expression of the REG IV gene in ulcerative colitis

Expression of the REG IV gene in ulcerative colitis

Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas

Developmental changes in hepatocyte growth factor mRNA and its receptor in rat liver, kidney and lung

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