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Toshikazu Nakamura - One of the best experts on this subject based on the ideXlab platform.

  • Hepatocyte Growth Factor: a regenerative drug for acute hepatitis and liver cirrhosis
    Regenerative medicine, 2007
    Co-Authors: Shinya Mizuno, Toshikazu Nakamura
    Abstract:

    Liver cirrhosis is a major cause of morbidity worldwide and is characterized by the loss of Hepatocytes with interstitial fibrosis. In this review, we discuss the potential uses of Hepatocyte Growth Factor for treating hepatic diseases, focusing on the molecular mechanisms whereby Hepatocyte Growth Factor reverses liver cirrhosis. Hepatic myofibroblasts play a central role in the development of liver cirrhosis, while myofibroblasts acquire c-Met. Using a rat model of liver cirrhosis, we recently delineated the direct effect of Hepatocyte Growth Factor toward myofibroblasts: the induction of apoptotic cell death associated with matrix degradation, the inhibition of overproliferation and the suppression of transforming Growth Factor-β1 production in myofibroblasts. Hepatocyte Growth Factor elicits mitogenic, anti-apoptotic and anti-inflammatory functions in Hepatocytes, therefore contributing to reversing liver dysfunction. Considering the insufficient production of Hepatocyte Growth Factor is responsible f...

  • Gene transfection of Hepatocyte Growth Factor attenuates the progression of cardiac remodeling in the hypertrophied heart
    The Journal of thoracic and cardiovascular surgery, 2005
    Co-Authors: Keiji Iwata, Toshikazu Nakamura, Yoshiki Sawa, Satoru Kitagawa-sakakida, Naomasa Kawaguchi, Nariaki Matsuura, Hikaru Matsuda
    Abstract:

    Objectives Hepatocyte Growth Factor plays a significant role in angiogenesis, anti-apoptosis, and anti-transforming Growth Factor-β1–mediated fibrosis in several organs. In this study, we investigated the effect of transfection of the Hepatocyte Growth Factor gene in attenuation of cardiac remodeling in the hypertrophied heart. Methods Two weeks after banding the ascending aorta of male Sprague-Dawley rats, a hemagglutinating virus of Japan-liposome complex with (H group) or without (C group) human Hepatocyte Growth Factor cDNA was transfected into the left ventricle wall by direct injection. The Hepatocyte Growth Factor, c-Met, and transforming Growth Factor-β1 mRNA levels in the left ventricle were then analyzed by real-time quantitative reverse-transcriptase polymerase chain reaction. Results Two weeks after transfection, the expression of transforming Growth Factor-β1 mRNA was significantly attenuated in the H group compared with the C group ( P P P Conclusions Our results demonstrated that gene transfection of Hepatocyte Growth Factor attenuated left ventricular diastolic dysfunction and cardiac fibrosis in association with a decrease in transforming Growth Factor-β1 in the rat heart subjected to pressure overload. Thus, the transfection of the Hepatocyte Growth Factor gene into the hypertrophied heart may be a strategy for the hypertrophied and failing heart even for cardiac surgery.

  • neutralization of Hepatocyte Growth Factor leads to retarded cutaneous wound healing associated with decreased neovascularization and granulation tissue formation
    Journal of Investigative Dermatology, 2003
    Co-Authors: Saho Yoshida, Yuji Yamaguchi, Satoshi Itami, Kunihiko Yoshikawa, Kunio Matsumoto, Yasuhiko Tabata, Toshikazu Nakamura
    Abstract:

    To elucidate biologic functions of Hepatocyte Growth Factor and the c-Met receptor in cutaneous wound healing, we analyzed expression and localization of Hepatocyte Growth Factor and c-Met receptor and used a strategy to neutralize endogenous Hepatocyte Growth Factor in a cutaneous wound healing model in mice. Following excision of full-thickness skin on the dorsum of mice, expression of both Hepatocyte Growth Factor and the c-Met receptor increased transiently in cutaneous tissues. Expressions of Hepatocyte Growth Factor increased as early as 2 d postwounding and reached a peak on day 2, whereas the c-Met receptor expression reached a peak 2–4 d postwounding. Immunolocalization of the c-Met receptor indicated that c-Met receptor expression was upregulated in keratinocytes, vascular endothelial cells, and myofibroblasts in granulation tissue, hence these are potential target cells of Hepatocyte Growth Factor. When normal rabbit IgG or neutralizing anti-Hepatocyte Growth Factor IgG was locally and continuously delivered to subcutaneous lesions, the number of capillary vessels decreased with the neutralization of Hepatocyte Growth Factor and there was an associated decreased expansion of granulation tissue. Likewise, retardation in re-epithelialization and the rate of wound closure occurred with neutralization of endogenous Hepatocyte Growth Factor on days 4 and 7 postwounding. Therefore, Hepatocyte Growth Factor is definitely involved in enhancing cutaneous wound healing processes, including re-epithelialization, neovascularization, and granulation tissue formation.

  • Hepatocyte Growth Factor in transgenic mice: Effects on Hepatocyte Growth, liver regeneration and gene expression
    Hepatology (Baltimore Md.), 1994
    Co-Authors: Goshi Shiota, Toshikazu Nakamura, Timothy C. Wang, Emmett V. Schmidt
    Abstract:

    Attention has recently been focused on Hepatocyte Growth Factor as a major candidate Factor in liver regeneration because it is the most potent known mitogen for Hepatocytes in vitro. However, Hepatocyte Growth Factor also displays diverse activities in vitro as scatter Factor, as an epithelial morphogen, as a pluripotent mitogen and as a Growth inhibitor. Consequently, we developed transgenic mice that exressed Hepatocyte Growth Factor under the control of albumin regulatory sequences to examine its in vivo role in Hepatocyte Growth. Hepatocytes of these mice expressed increased levels of Hepatocyte Growth Factor as an autocrine Growth Factor

  • Heparin‐Hepatocyte Growth Factor complex with low plasma clearance and retained Hepatocyte proliferating activity
    Hepatology (Baltimore Md.), 1994
    Co-Authors: Yukio Kato, Toshikazu Nakamura, Ke-xin Liu, Yuichi Sugiyama
    Abstract:

    Because Hepatocyte Growth Factor is known to have affinity for heparin, we studied the binding isotherm and found that Hepatocyte Growth Factor has a high-affinity binding site for 35S-heparin with an equilibrium dissociation constant of approximately 0.6 nmol/L. We then analyzed the pharmacokinetic behavior of the heparin–Hepatocyte Growth Factor complex in rats. The area under the plasma concentration-time profiles of trichloroacetic acid–precipitable radioactivities from 0 to 30 min after the intravenous administration of the heparin–125I-Hepatocyte Growth Factor complex was approximately three times that after the administration of 125I-Hepatocyte Growth Factor only. Because we previously demonstrated that the liver is the major clearance organ for Hepatocyte Growth Factor, the hepatic uptake of 125I-Hepatocyte Growth Factor and the heparin–125I-Hepatocyte Growth Factor complex was compared. The liver-to-plasma concentration ratio after the intravenous administration of the complex was half that after the administration of 125I-Hepatocyte Growth Factor only. Furthermore, the steady state hepatic extraction ratio of 125I-Hepatocyte Growth Factor in perfused rat liver decreased depending on the heparin concentration. In addition, the biological activity of the complex was examined by assessing the 125I-deoxyuridine incorporation in cultured rat Hepatocytes. Although the half-effective concentration of Hepatocyte Growth Factor increased slightly–namely, two to three times in the presence of heparin compared with that in its absence–the maximal activity was not changed. We conclude that the heparin–Hepatocyte Growth Factor complex, which retains biological activity, exhibits much lower clearances for hepatic uptake and plasma disappearance than Hepatocyte Growth Factor itself. The heparin–Hepatocyte Growth Factor complex may thus be utilized as a drug delivery system for Hepatocyte Growth Factor. (Hepatology 1994;20:417–424.)

Y Tomoda - One of the best experts on this subject based on the ideXlab platform.

  • Hepatocyte Growth Factor in human amniotic fluid promotes the migration of fetal small intestinal epithelial cells
    American Journal of Obstetrics and Gynecology, 1998
    Co-Authors: M Okamura, A Itakura, O Kurauchi, S Morikawa, N Suganuma, S Mizutani, Y Tomoda
    Abstract:

    Abstract OBJECTIVE: Previously we reported on the abundant existence of Hepatocyte Growth Factor in amniotic fluid. This study was conducted to clarify the effects of Hepatocyte Growth Factor in amniotic fluid on fetal intestinal epithelial cells. STUDY DESIGN: Amniotic fluid samples were obtained from 22 cases at various gestational ages. The effects of amniotic fluid and recombinant human Hepatocyte Growth Factor on proliferation, migration, and morphogenesis of intestine 407 cells (a cell line derived from fetal intestinal epithelial cells) were investigated. RESULTS: The mobility of intestine 407 cells was stimulated by amniotic fluid in proportion to the concentration of Hepatocyte Growth Factor in amniotic fluid with the same effect observed with recombinant human Hepatocyte Growth Factor. This activity was neutralized by addition of antihuman Hepatocyte Growth Factor antibody. Neither increased deoxyribonucleic acid synthesis nor morphogenesis in response to amniotic fluid was identified under the conditions used. CONCLUSIONS: Amniotic fluid stimulates intestinal epithelial cell migration by way of Hepatocyte Growth Factor in amniotic fluid during development of the fetal intestine. (Am J Obstet Gynecol 1998;178:175-9.)

  • Levels of Hepatocyte Growth Factor in maternal serum and amniotic fluid.
    American journal of obstetrics and gynecology, 1995
    Co-Authors: N Horibe, T Okamoto, A Itakura, T Nakanishi, T Suzuki, S Kazeto, Y Tomoda
    Abstract:

    The purpose of our study was to investigate Hepatocyte Growth Factor levels in maternal serum and amniotic fluid during pregnancy. We also demonstrated production and secretion of Hepatocyte Growth Factor by placenta and amnion at different stages of gestation. Hepatocyte Growth Factor levels in maternal serum (n = 219), cord blood (n = 20), and amniotic fluid samples (n = 90) were measured by an enzyme-linked immunosorbent assay. The secretion of Hepatocyte Growth Factor by placenta and amnion was evaluated by measuring the amount released into the culture supernatant. Most Hepatocyte Growth Factor levels in maternal serum were below the detection limit before 10 weeks of pregnancy. Levels increased significantly thereafter and continued to increase until term. On the other hand, levels in amniotic fluid were significantly higher between 20 and 29 weeks of gestation than after 30 weeks. Hepatocyte Growth Factor secretion from the placental tissue per weight seemed unchanged throughout pregnancy. Its secretion from amnion was, however, approximately 300 to 400-fold higher in the second trimester compared with that at term. Both placenta and amnion produce and secrete Hepatocyte Growth Factor, suggesting its role in fetal Growth and the Growth and differentiation of placenta.

  • Levels of Hepatocyte Growth Factor in maternal serum and amniotic fluid
    American Journal of Obstetrics and Gynecology, 1995
    Co-Authors: N Horibe, T Okamoto, A Itakura, T Nakanishi, T Suzuki, S Kazeto, Y Tomoda
    Abstract:

    Abstract OBJECTIVE: The purpose of our study was to investigate Hepatocyte Growth Factor levels in maternal serum and amniotic fluid during pregnancy. We also demonstrated production and secretion of Hepatocyte Growth Factor by placenta and amnion at different stages of gestation. STUDY DESIGN: Hepatocyte Growth Factor levels in maternal serum ( n = 219), cord blood ( n = 20), and amniotic fluid samples ( n = 90) were measured by an enzyme-linked immunosorbent assay. The secretion of Hepatocyte Growth Factor by placenta and amnion was evaluated by measuring the amount released into the culture supernatant. RESULTS: Most Hepatocyte Growth Factor levels in maternal serum were below the detection limit before 10 weeks of pregnancy. Levels increased significantly thereafter and continued to increase until term. On the other hand, levels in amniotic fluid were significantly higher between 20 and 29 weeks of gestation than after 30 weeks. Hepatocyte Growth Factor secretion from the placental tissue per weight seemed unchanged throughout pregnancy. Its secretion from amnion was, however, approximately 300 to 400-fold higher in the second trimester compoared with that at term. CONCLUSION: Both placenta and amnion produce and secrete Hepatocyte Growth Factor, suggesting its role in fetal Growth and the Growth and differentiation of placenta.

Yi Yang - One of the best experts on this subject based on the ideXlab platform.

Raphael E. Pollock - One of the best experts on this subject based on the ideXlab platform.

M Okamura - One of the best experts on this subject based on the ideXlab platform.

  • Hepatocyte Growth Factor in human amniotic fluid promotes the migration of fetal small intestinal epithelial cells.
    American journal of obstetrics and gynecology, 1998
    Co-Authors: M Okamura, O Kurauchi, A Itakura, S Morikawa, N Suganuma, S Mizutani, Y Tomoda
    Abstract:

    Previously we reported on the abundant existence of Hepatocyte Growth Factor in amniotic fluid. This study was conducted to clarify the effects of Hepatocyte Growth Factor in amniotic fluid on fetal intestinal epithelial cells. Amniotic fluid samples were obtained from 22 cases at various gestational ages. The effects of amniotic fluid and recombinant human Hepatocyte Growth Factor on proliferation, migration, and morphogenesis of intestine 407 cells (a cell line derived from fetal intestinal epithelial cells) were investigated. The mobility of intestine 407 cells was stimulated by amniotic fluid in proportion to the concentration of Hepatocyte Growth Factor in amniotic fluid with the same effect observed with recombinant human Hepatocyte Growth Factor. This activity was neutralized by addition of antihuman Hepatocyte Growth Factor antibody. Neither increased deoxyribonucleic acid synthesis nor morphogenesis in response to amniotic fluid was identified under the conditions used. Amniotic fluid stimulates intestinal epithelial cell migration by way of Hepatocyte Growth Factor in amniotic fluid during development of the fetal intestine.

  • Hepatocyte Growth Factor in human amniotic fluid promotes the migration of fetal small intestinal epithelial cells
    American Journal of Obstetrics and Gynecology, 1998
    Co-Authors: M Okamura, A Itakura, O Kurauchi, S Morikawa, N Suganuma, S Mizutani, Y Tomoda
    Abstract:

    Abstract OBJECTIVE: Previously we reported on the abundant existence of Hepatocyte Growth Factor in amniotic fluid. This study was conducted to clarify the effects of Hepatocyte Growth Factor in amniotic fluid on fetal intestinal epithelial cells. STUDY DESIGN: Amniotic fluid samples were obtained from 22 cases at various gestational ages. The effects of amniotic fluid and recombinant human Hepatocyte Growth Factor on proliferation, migration, and morphogenesis of intestine 407 cells (a cell line derived from fetal intestinal epithelial cells) were investigated. RESULTS: The mobility of intestine 407 cells was stimulated by amniotic fluid in proportion to the concentration of Hepatocyte Growth Factor in amniotic fluid with the same effect observed with recombinant human Hepatocyte Growth Factor. This activity was neutralized by addition of antihuman Hepatocyte Growth Factor antibody. Neither increased deoxyribonucleic acid synthesis nor morphogenesis in response to amniotic fluid was identified under the conditions used. CONCLUSIONS: Amniotic fluid stimulates intestinal epithelial cell migration by way of Hepatocyte Growth Factor in amniotic fluid during development of the fetal intestine. (Am J Obstet Gynecol 1998;178:175-9.)