The analysis of liver-to-pancreas reprogramming based on cellular interaction

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591516
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Shinshu University
• Principal Investigator: KOBAYASHI Akira 信州大学, 医学部, 准教授 (90334903)
• Co-Investigator(Kenkyū-buntansha): MOTOYAMA Hiroaki 信州大学, 医学部附属病院, 助教 (20569587) ; MIYAGAWA Shinichi 信州大学, 医学部, 教授 (80229806)
• Project Period (FY): 2010 – 2012
• Keywords: 再生医療 / 遺伝子治療

Research Abstract

We introduced Pdx1 and Ngn3 into regenerative liver using non-viral gene transfer technique. Co-expression of Pdx1 and Ngn3 activated the transcription of various islet-related genes, and induced insulin synthesis in the liver. Futhermore, it was suggested that this reprogramming was enhanced by co-expression of triple factors adding v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA).In conclusion, the reprogramming will occur even in vivo without the need for viral vectors. Further investigation might be needed to optimize the combination of transgene.

Research Products

• [Journal Article] Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells. (2012)
  • Author(s): Gui A, Kobayashi A, Motoyama H, Kitazawa M, Takeoka M, Miyagawa S.
  • Journal Title: BMC Cancer Volume: 12 Pages: 179
  • DOI: DOI:10.1186/1471-2407-12-179.
  • Peer Reviewed
• [Journal Article] Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet. (2012)
  • Author(s): Akita S, Kubota K, Kobayashi A, Misawa R,Shimizu A, Nakata T, Yokoyama T, Takahashi M, Miyagawa S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 420(4) Pages: 743-9
  • DOI: DOI:10.1016/j.bbrc.2012.03.060.
  • Peer Reviewed
• [Journal Article] Essential role of gastric gland mucin in preventing gastric cancer in mice. (2012)
  • Author(s): Karasawa F, Shiota A, Goso Y, Kobayashi M, Sato Y, Masumoto J, Fujiwara M, Yokosawa S, Muraki T, Miyagawa S, Ueda M, Fukuda MN, Fukuda M, Ishihara K, Nakayama J.
  • Journal Title: J Clin Invest. Volume: 122(3) Pages: 923-34
  • DOI: DOI:10.1172/JCI59087.
  • Peer Reviewed
• [Journal Article] Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling. (2011)
  • Author(s): Arai T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Iinuma N, Iesato Y,Koyama T, Yoshizawa T, Uetake R, Yamauchi A, Yang L, Kawate H, Ogawa S, Kobayashi A, Miyagawa S, Shindo T.
  • Journal Title: Peptides. Volume: 32(9) Pages: 1855-65
  • DOI: DOI:10.1016/j.peptides.2011.07.005.
  • Peer Reviewed
• [Journal Article] COP35, a cholangiocarcinoma-binding oligopeptide, interacts with the clathrin heavy chain accompanied by GRP78. (2011)
  • Author(s): Kitahara H, Masumoto J, Parker AL, Maruta F, Kubo N, Shimizu A, Akita N, Miwa S, Kobayashi N, Nakayama J, Miyagawa S
  • Journal Title: Mol Cancer Res. Volume: 9(6) Pages: 688-701
  • DOI: DOI:10.1158/1541-7786.MCR-10-0470.
  • Peer Reviewed
• [Journal Article] Clinicopathological features of hepatitis C virus disease after living donor liver transplantation: relationship with in situ hybridisation data. (2011)
  • Author(s): Masuda Y, Nakazawa Y, Matsuda K, Sano K, Mita A, Ohno Y, Urata K, Ikegami T, Miwa S, Miyagawa S.
  • Journal Title: Pathology Volume: 43(2) Pages: 156-60
  • DOI: DOI:10.1097/PAT.0b013e32834317ed.
  • Peer Reviewed
• [Journal Article] Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells. (2010)
  • Author(s): Sakai H, Tagawa Y, Tamai M, Motoyama H, Ogawa S, Soeda J, Nakata T, Miyagawa S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 403(3-4) Pages: 403(3-4)
  • DOI: DOI:10.1016/j.bbrc.2010.11.021.
  • Peer Reviewed
• [Journal Article] Adrenomedullin in sinusoidal endothelial cells play protective roles against cold injury of liver. (2010)
  • Author(s): Iinuma N, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Arai T, Yoshizawa T, Koyama T, Uetake R, Kawate H, Muto S, Tagawa Y, Miyagawa S, Shindo T.
  • Journal Title: Peptides. Volume: 31(5) Pages: 865-71
  • DOI: DOI:10.1016/j.peptides.2010.01.011.
  • Peer Reviewed
• [Presentation] Liver-to-pancreas reprogramming - 膵切除後内分泌機能不全への応用 - (2013)
  • Author(s): 本山博章
  • Organizer: 第113回日本外科学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2013-04-12
• [Presentation] Induction of pancreatic β-like cells from hepatic cells. (2012)
  • Author(s): 本山博章
  • Organizer: 第35回日本分子生物学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] A Useful Non-viral Procedure to Induce Liver-to-pancreas Reprogramming to Complement Post-operative Pancreatic Endocrine Dysfunction (2011)
  • Author(s): 本山博章
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡
  • Year and Date: 2011-07-17
• [Presentation] Liver-to-pancreas reprogramming 膵切除後内分泌機能不全への応用 (2011)
  • Author(s): 本山博章
  • Organizer: 第66回日本消化器外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-07-15
• [Presentation] An excellent non-viral procedure to induce liver-to-pancreas reprogramming to complement post-operative pancreatic endocrine dysfunction. (2010)
  • Author(s): 本山博章
  • Organizer: 8th Catholic International Stem Cell Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-10-02