2007 Fiscal Year Final Research Report Summary
Regulation of tissue regeneration and homeostasis through ON-OFFcontrol of the Met/HGF receptor
| Project/Area Number |
18570127
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Kanazawa University (2007)
Osaka University (2006) |
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Principal Investigator |
MATSUMOTO Kunio Kanazawa University, Cancer Research Insitute, 教授 (90201780)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Takahiro Kanazawa University, Cancer Research Institute, 助教 (70414018)
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| Project Period (FY) |
2006 – 2007
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| Keywords | HGF / Met / contact inhibition / tissue regeneration / knockout mouse / protein tyrosine phosnhatase / tyrosine kinase / growth factor |
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| Research Abstract |
HGF (hepatocyte growth factor) and Met/HGF receptor tyrosine kinase play important roles in tissue regeneration. In non-injured normal tissues, Met activation/tyrosine phosphorylation is suppressed even following binding with HGF. Thus, HGF-dependent Met receptor activation may be regulated by not only HGF-binding but also cellular context such as cell-cell contact and cellular injury. In this research, suppressive mechanisms of Met activation through cell-cell contact and Ser985 phosphorylation in the juxtamembrane domain of the Met were investigated.
1. In hepatocytes cultured at a sparse cell density, HGF induced prolonged Met activation and a marked mitogenic response. In contrast, HGF induced transient Met activation but failed to induce mitogenic response in confluent hepatocytes with tight cell-cell contact. Expression of the protein tyrosine phosphatase, LAR increased following HGF-stimulation specifically in confluent hepatocytes. LAR associated with Met and dephosphorylated ty
… More
rosine-phosphorylated Met. Thus functional association of LAR and Met underlies the inhibitory mechanism by which HGF-dependent Met activation is suppressed by cell-cell contact.
2. In hepatocytes in culture, HGF-dependent Met tyrosine phosphorylation/activation was inhibited when Ser985 was phosphorylated. In the normal liver, Met Ser985 was phosphorylated, however, Ser985 was dephosphorylated after hepatic injury such as partial hepatectomy. In reciprocal manner to Ser985 phosphorylation, Met was activated after hepatic injury. The results suggest that Ser985 in the juxtamembrane domain of Met is regulated by tissue injury and that Ser985 phosphorylation in the juxtamembrane domain of Met may be a mechanism by which HGF-dependent Met activation is suppressed in non-injured organs. Because Met receptor deleted with the juxtamembrane is naturally expressed as a splicing variant, the juxtamembrane of the Met may play an important role in regulation of HGF-dependent Met activation in response to tissue injury.
3. Physiological significance of the juxtamembrane domain of Met in the development and tissue regeneration is investigated using the transgenic mice which express only variant Met deleted with the juxtamembrane domain. Less
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[Journal Article] Generation of engineered recombinant hepatocyte growth factor cleaved and activated by Genenase I2008
Author(s)
Hayata, D., Fukuta, K., Matsumoto, K., Adachi, E., Hanada, K., Adachi, K., Nakamura, T
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Journal Title
J Biotechnol 133
Pages: 478-485
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hepatocyte growth factor improves synaptic localization of the NMDA receptor and intracellular signaling after excitotoxic injury in cultured hippocampal neurons2008
Author(s)
Akita, H., Takagi, N., Ishihara, N., Takagi, K., Murotomi, K., Funakoshi, H., Matsumoto, K., Nakamura, T., Takeo, S
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Journal Title
Exp Neurol 210(1)
Pages: 83-94
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice2008
Author(s)
Ito, W., Tanimoto, M., Ono, K., Mizuno, S., Yoshida, A., Koga, H., Fuchimoto, Y., Kondo, N., Tanimoto, Y., Kiura, K., Matsumoto, K., Kataoka, M., Nakamura, T., Gelfand, E., Kanehiro, A
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Journal Title
Int. Arch. Allergy Immunol 145
Pages: 324-339
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A genomic analysis of adult T-cell leukemia2007
Author(s)
Choi, Y. L., Tsukasaki, K., O'neill, M., C., Yamada, Y., Onimaru, Y., Matsumoto, K., Ohashi, J., Yamashita, Y., Tsutsumi, S., Kaneda, R., Takada, S., Aburatani, H., Kamihira, S., Nakamura, T., Tomonaga, M., Mano, H
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Journal Title
Oncogene 26
Pages: 1245-1255
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A genomic analysis of adult T-cell leukemia2007
Author(s)
Choi, Y.L., Tsukasaki, K., O'neill, M.C., Yamada, Y., Onimaru, Y., Matsumoto, K., Ohashi, J., Yamashita, Y., Tsutsumi, S., Kaneda, R., Takada, S., Aburatani, H., Kamihira, S., Nakamura, T., Tomonaga, M., Mano, H
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Journal Title
Oncogene 26
Pages: 1245-1255
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Stimulation of Hepatocyte Growth Factor Production by Heparin-derived Oligosaccharides2007
Author(s)
Sakiyama, R., Fukuta, K., Matsumoto, K., Furukawa, M., Takahashi, Y., Nakamura, T
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Journal Title
J. Biochem 141
Pages: 653-660
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] NK4, an antagonist of hepatocyte growth factor (HGF), inhibits growth of multiple myeloma cells in vivo ; molecular targeting of angiogenic growth factor2007
Author(s)
Du, W., Hattori, Y., Yamada, T., Matsumoto, K., Nakamura, T., Sagawa, M., Otsuki, T., Niikura, T., Nukiwa, T., Ikeda, Y
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Journal Title
Blood 109
Pages: 3042-3049
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hepatocyte growth factor prevents pulmonary ischemia-reperfusion injury in mice2007
Author(s)
Makiuchi, A., Yamaura, K., Mizuno, S., Matsumoto, K., Nakamura, T., Amano, J., Ito, K
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Journal Title
J. Heart Lung Transplant
Pages: 935-943
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells2007
Author(s)
Kanehira, M., Xin, H., Hoshino, K., Maemondo, M., Mizuguchi, H., Hayakawa, T., Matsumoto, K., Nakamura, T., Nukiwa, T., Saijo, Y
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Journal Title
Cancer Gene Ther 14
Pages: 894-903
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hepatocyte growth factor promotes the number of PSD-95 clusters in young hippocampal neurons2007
Author(s)
Nakano, M., Takagi, N., Takagi, K., Funakoshi, H., Matsumoto, K., Nakamura, T., Takeo, S
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Journal Title
Exp. Neurol 207(2)
Pages: 195-202
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Preclinical study of a "tailor-made" combination of NK4-expressing gene therapy and gefitinib (ZD1839, Iressatrade mark) for disseminated peritoneal scirrhous gastric cancer2006
Author(s)
Narniki, Y., Namiki, T., Yoshida, H., Date, M., Yashiro, M., Matsumoto, K., Nakamura, T., Yanagihara, K., Tada, N., Satoi, J., Fujise, K
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Journal Title
Int. J. Cancer 118
Pages: 1545-1555
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival2006
Author(s)
Ogura, Y., Mizumoto, K., Nagai, E., Murakami, M., Inadome, N., Saimura, M., Matsumoto, K., Nakamura, T., Maemondo, M., Nukiwa, T., Tanaka, M
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Journal Title
Cancer Gene Ther 13
Pages: 520-529
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Involvement of hepatocyte growth factor in the development of bone metastasis of a mouse mammary cancer cell line, BALB/c-MC2006
Author(s)
Ono, K., Kamiya, S., Akatsu, T., Nakamura, C., Li, M., Amizuka, N., Matsumoto, K., Nakamura, T., Kugai, N., Wada, S
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Intraventricular administration of hepatocyte growth factor treats mouse communicating hydrocephalus induced by transforming growth factor-β12006
Author(s)
Tada, T., Zhan, H., Tanaka, Y., Hongo, K., Matsumoto, K., Nakamura, T
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Journal Title
Neurobiol. Disease 21
Pages: 576-586
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Angiogenic and antifibrotic actions of hepatocyte growth factor improve cardiac dysfunction in porcine ischemic cardiomyopathy2006
Author(s)
Azuma, J., Taniyama, Y., Takeya, Y., Iekushi, K., Aoki, M., Dosaka, N., Matsumoto, K., Nakamura, T., Ogihara, T., Morishita, R
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Journal Title
Gene Therapy 13
Pages: 1206-1213
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Blockage of HGF/c-Met system by gene therapy (adenovirus-mediated NK4 gene) suppresses hepatocellular carcinoma in mice2006
Author(s)
Son, G., Hirano, T., Seki, E., Iimuro, Y., Nukiwa, T., Matsumoto, K., Nakamura, T., Fujimoto, J
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Journal Title
J. Hepatol 45
Pages: 688-695
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prevention of apoptosis-inducing factor translocation is a possible mechanism for protective effects of hepatocyte growth factor against neuronal cell death in the hippocampus after transient forebrain ischemia2006
Author(s)
Niimura, M., Takagi, N., Takagi, K., Mizutani, R., Ishihara, N., Matsumoto, K., Funakoshi, H., Nakamura, T., Takeo, S
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Journal Title
J. Cereb. Blood Flow Metab 26
Pages: 1354-1365
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity2006
Author(s)
Niimura, M., Takagi, N., Takagi, K., Mizutani, R., Tanonaka, K., Funakoshi, H., Matsumoto, K., Nakamura, T., Takeo, S
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Journal Title
Neurosci. Lett. 407
Pages: 136-140
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Model of vasculogenesis from embryonic stem cells for vascular research and regenerative medicine2006
Author(s)
Nakagami, H., Nakagawa, N., Takeya, Y., Kashiwagi, K., Ishida, C., Hayashi, S., Aoki, M., Matsumoto, K., Nakamura, T., Ogihara, T., Morishita, R
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Journal Title
Hypertension 48
Pages: 112-119
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hepatocyte growth factor attenuates cerebral ischemia-induced increase in permeability of the blood-brain barrier and decreases in expression of tight junctional proteins in cerebral vessels2006
Author(s)
Date, I., Takagi, N., Takagi, K., Tanonaka, K., Funakoshi, H., Matsumoto, K., Nakamura, T., akeo, S
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Journal Title
Neurosci. Lett. 407
Pages: 141-145
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Reduction of fibrosis in a rat model of non-alcoholic steatohepatitis cirrhosis by human HGF gene transfection using electroporation
Author(s)
Kiyama, S., Yamada, T., Iwata, H., Sekino, T., Matsuo, H., Yoshida, N., Miyahara, T., Umeda, Y., Matsuno, Y., Kimura, M., Matsumoto, K., Nakamura, T., Takemura, H
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Journal Title
J. Gastroenterol. Hepatol (in press)
Description
「研究成果報告書概要(欧文)」より
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