Establishment of Therapeutic Approaches by Modification of the Activin-Follistatin System.
Project/Area Number |
18390273
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Endocrinology
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Research Institution | Gunma University |
Principal Investigator |
KOJIMA Itaru Gunma University, IMCR, Professor (60143492)
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Co-Investigator(Kenkyū-buntansha) |
AOKI Fumiaki Gunma University, Graduate School of Medicine, Fellow (50420089)
YAMADA Satoko Gunma University, IMCR, COE Assistant Professor (80420090)
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Project Period (FY) |
2006 – 2007
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Project Status |
Completed (Fiscal Year 2007)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2007: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2006: ¥10,400,000 (Direct Cost: ¥10,400,000)
|
Keywords | activin / follistatin / diabetes / fibrosis / regeneration / 細胞増殖 / 分化 / 肝再生 / 血管新生 / 血管内皮 / 管腔形成 |
Research Abstract |
1) We previously reported that follistatin accelerates liver regeneration after partial hepatectomy. When massive hepatectomy is performed, the function of the remnant liver is critical. Since rapidly growing cells lack mature cell functions, it is an interesting question whether or not acceleration of hepatocyte growth is actually beneficial. To address this issue, we compared the effect of follistatin and activin A on remnant liver function in 90% hepatectomized rats. To our surprise, administration of low dose of activin A was more beneficial in terms of remnant liver function. 2) We previously reported the efficacy of activin A in stimulating regeneration of pancreatic beta cells. However, activin A has a proapoptotic action in many types of cells, which may be a disadvantage for clinical use. We therefore searched for a new factor which has an activin-like differentiation-inducing activity without promoting apoptosis. In this regard, we found conophylline, a new vinca alkaloid, which reproduces the action of activin A but does not induce apoptosis. Conophylline was effective in promoting differentiation of pancreatic progenitors to beta cells in vitro and in vivo.
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Report
(3 results)
Research Products
(110 results)
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[Journal Article] Proteomic analysis identifies proteins that continue to grow hepatic stem-like cells without differentiation2008
Author(s)
Saheki, T., Ito, H., Sekiguchi, A., Sugiyama, T., Izumi, T. and Kojima, I.
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Journal Title
Cytotechnology (in press)
Description
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[Journal Article] A betacellulin mutant promotes differentiation of pancreatic acinar AR42J cells into insulin-producing cells with low affinity of binding to ErbB12008
Author(s)
Nagaoka, T., Fukuda, T., Hashizume, T., Nishiyama, T., Tada, H., Yamada, H., Salomon, D. S., Yamada, S., Kojima, L, and Seno, M.
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[Journal Article] Reversal of streptozotocin-induced hyperglycemia by continuous supply of betacellulin in mice2008
Author(s)
Yamamoto, Y., Yamada, S., Kodera, T., Hara, A., Motoyoshi, K., Tanaka,Y. Nagaoka, T., Seno, M. and Kojima, I.
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[Journal Article] Conophylline and betacellulin-□4: effective combination to promote differentiation of pancreatic β cells2007
Author(s)
Kitamura, R., Ogata, T., Tanaka, Y., Seno, M., Umezawa, K., Taki, I., and Kojima, I.
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Journal Title
Endocrine J 54
Pages: 255-264
Description
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[Journal Article] MafA regulates expression of genes important to islet beta cell function2007
Author(s)
Matsuoka, T. A., Kaneto, H., Stein, R., Miyatsuka, T., Kawamori, D., Henderson,E., Kojima, I., Mastuhisa, M., Hon, M. and Yamasaki, Y.
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Journal Title
Mol. Endocrinol 21
Pages: 2764-2774
Description
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[Journal Article] Ptfl and RBP-J cooperate in activati ng Pdxl gene expression through binding to Area III2007
Author(s)
Miyatsuka, T., Matsuoka, T. A., Shiraiwa, T., Yamamoto, T., Kojima, I. and Kaneto, H.
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Journal Title
Biochem. Biophys. Res. Commun 362
Pages: 905-909
Description
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[Journal Article] 糖尿病の再生医療2006
Author(s)
小寺力、小島至
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Journal Title
Diabetes Frontier 17
Pages: 308-313
Description
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Peer Reviewed
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[Journal Article] Activin A-induced expression of PAX4 in AR42J-B13 cells involves the increase in transactivation of E47/E122006
Author(s)
Kanno, R., Ogihara, T., Igarashi, Y., Tanaka, Y., Smith, S. B., Kojima, I., German, M. S., Kawamori, R. and Watada, H.
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Journal Title
Biochim. Biochem. Acta 1759
Pages: 44-50
Description
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[Journal Article] Development of a novel β cell specific promotor system for the identification of insulin producing cells in in vitro cell cultures2006
Author(s)
Fukazawa, T., Matsuoka, J., Naomoto, Y., Nakai, T., Darbin, M., Kojima, I., Lakey, JRT., Tanaka, N.
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Journal Title
Exp. Cell Res 312
Pages: 3404-12
Description
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[Journal Article] GLP-1 activates protein kinase C through Ca^<2+> - dependent activation of phospholipase C in insulin-secreting cells2006
Author(s)
Suzuki, Y., Zhang, H., Saito, N., Kojima, I., Urano, T. and Mogami, H.
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Journal Title
J. Biol. Chem 281
Pages: 28499-507
Description
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[Journal Article] In vitro transdifferentiation of mature hepatocytes into insulin-producing cells2006
Author(s)
Yamada, S., Yamamoto, Y., Nagasawa, M., Hara, A., Kodera, T. and Kojima, I.
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Journal Title
Endocrine J 53
Pages: 789-795
NAID
Description
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[Journal Article] Activin A-induced expression of PAX4 in AR42J-B13 cells involves the increase in transactivation of E47/E12.2006
Author(s)
Kanno, R., Ogihara, T., Igarashi, Y., Tanaka, Y., Smith, S.B., Kojima, I., German, M.S., Kawamori, R., Watada, H.
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Journal Title
Biochim. Biochem. Acta 1759
Pages: 44-50
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[Journal Article] GLP-1 activates protein kinase C through Ca2+-dependent activation of phospholipase C in insulin-secreting cells.2006
Author(s)
Suzuki, Y., Zhang, H., Saito, N., Kojima, I., Urano, T., Mogami, H.
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Journal Title
J. Biol. Chem 281
Pages: 28499-28507
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[Journal Article] Development of a novel β cell specific promoter system for the identification of insulin producing cells in vitro cell cultures.2006
Author(s)
Fukazawa, T., Matsuoka, J., Naomoto, Y., Nakai, T., Darbin, M., Kojima, I., Lakey, JRT., Tanaka, N.
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Journal Title
Exp. Cell Res. 312
Pages: 3404-3412
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[Journal Article] In vitro transdifferentiation of mature hepatocytes into insulin-producing cells.2006
Author(s)
Yamada, S., Yamamoto, Y., Nagasawa, M., Hara, A., Kodera, T., Kojima, I.
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Journal Title
Endocrine J 53
Pages: 785-795
NAID
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[Journal Article] A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-δ4
Author(s)
Hisanaga, E., Park, K. Y., Yamada, S., Hashimoto, H., Takeuchi, T, Mori, M., Seno, M., Umezawa, K., Takei, I. and kojima, I.
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[Journal Article] Conophylline and betacellulin-d4 : effective combination to promote differentiation of pancreatic β cells.
Author(s)
Kiamura, R., Ogata, T., Tanaka, Y., Seno, M., Umezawa, K., Taki, I., Kojima, I.
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Journal Title
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[Presentation] 膵β細胞の再生と分化誘導因子2007
Author(s)
小島 至
Organizer
第1回慶応大学ハイテクリサーチシンポジウム
Place of Presentation
横浜
Year and Date
2007-12-08
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[Presentation] Effect of Extracellular Matrix on Differentiation of AR42J Cells2007
Author(s)
Hamamoto, K., Yamada, S., Yamamoto, Y., Kodera, K., Hara, A., Seno, M., Kojima, I.
Organizer
50th Japan Diabetes Society
Place of Presentation
Sendai
Description
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[Presentation] Treatment of Type 2 Diabetes By Transduction of BTC Gene2007
Author(s)
Yamamoto, Y., Yamada, S., Kodera, T., Hara, A., Tanaka, Y., Motoyoshi, K., Seno, M., Kojima, I.
Organizer
50th Japan Diabetes Society
Place of Presentation
Sendai
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[Presentation] Effect of Conophylline and betacellulin-δ4 in Type Diabetic Model2007
Author(s)
Kodera, T., Yamamoto, Y., Hara, A., Yamada, S., Tanaka, Y., Watanabe, Y., Seno, M., Takei, I., Umezawa, K, Kojima, I.
Organizer
50th Japan Diabetes Society
Place of Presentation
Sendai
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[Presentation] Treatment of Type 2 Diabetes Using Conophylline and betacellulin -δ42006
Author(s)
Kodera, T., Yamamoto, Y., Hara, A., Yamada, S., Tanaka, Y., Watanabe, Y., Seno, M.,Umezawa, K., Takei, I., Kojima, I.
Organizer
49th Japan Diabetes Society
Place of Presentation
Tokyo
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[Presentation] Regeneration of β cells by Transduction of Mature BTC Gene2006
Author(s)
Yamamoto, Y., Yamada, S., Hara, A., Nagaoka, T., Kitamura, R., Kodera, T., Yanaka, Y., Motoyoshi, K., Seno M., Kojima I.
Organizer
49th Japan Diabetes Society
Place of Presentation
Tokyo
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[Presentation] Differentiation of Mouse Mesenchymal Cells to Insulin-secreting Cells2006
Author(s)
Hisanaga, E., Yamada, S., Yamamoto, Y., Okada, S., Shimizu, H., Mori, M., Kojima, I.
Organizer
49th Japan Diabetes Society
Place of Presentation
Tokyo
Description
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[Presentation] TRPV2 Expressed in MIN6 Cells2006
Author(s)
Hisanaga, E., Nagasawa, M., Okada, S., Shimizu, H., Mori, M., Kojima, I.
Organizer
49th Japan Diabetes Society
Place of Presentation
Tokyo
Description
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[Presentation] Proteome Analysis of HSL Cells2006
Author(s)
Ito, H., Saeki, T., Sekiguchi, A., Nishina, A., Izumi, T., Sugiyama, T. Kojima, I.
Organizer
Japanese Molecular Biology Forum
Place of Presentation
Nagoya
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