Molecular basis of proliferative diseases associated with BMP receptor mutations

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390059
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: University of Toyama
• Principal Investigator: BEPPU Hideyuki 富山大学, 大学院・医学薬学研究部(医学), 准教授 (20550479)
• Project Period (FY): 2010 – 2012
• Keywords: 大腸ポリープ / 上皮間質相互作用 / BMP / 受容体 / 遺伝子改変マウス

Research Abstract

BMP signaling is transduced by BMP receptors （e.g., BMPR2), which are located at cell membrane. Mutations of BMP receptor genes are known to cause pulmonary hypertension, congenital heart defects, and juvenile polyposis syndrome. We investigated molecular mechanism, by which BMP receptor mutations develop ccell-proliferative diseases, using BMPR2-deficient mice and fibroblast cells isolated from the mice. We found that BMPR2-deficient fibroblast cells promoted proliferation of epithelial cells. Also, suppression of BMP signaling augmented TNF-induced NK-kB activation. These results suggest that increased inflammatory response may play an important role in the pathogenesis of the diseases caused by the BMP receptor mutations

Research Products

• [Journal Article] Basolateral BMP Signaling in Polarized Epithelial Cells (2013)
  • Author(s): Saitoh M, Shirakihara T, Fukasawa A, Horiguchi K, Sakamoto K, Sugiya H, Beppu H, Fujita Y, Morita I, Miyazono K, Miyazawa K
  • Journal Title: PLoS One Volume: 8(5) Pages: e62659
  • DOI: DOI:10.1371/journal.pone.0062659
  • Peer Reviewed
• [Journal Article] Constitutively Active ALK2 Receptor Mutants Require Type II Receptor Cooperation (2013)
  • Author(s): Bagarova J, Vonner AJ, Armstrong KA, Borgermann J, Lai CS, Deng DY, Beppu H, Alfano I, Filippakopoulos P, Morrell NW, Bullock AN, Knaus P, Mishina Y, Yu PB
  • Journal Title: Mol Cell Biol Volume: 33(12) Pages: 2413-24
  • DOI: DOI:10.1128/MCB.01595-12
  • Peer Reviewed
• [Journal Article] Smad7-modified alleles by various gene-targeting strategies (2013)
  • Author(s): Beppu H
  • Journal Title: J Biochem Volume: 153(5) Pages: 399-401
  • DOI: DOI:10.1093/jb/mvt020
  • Peer Reviewed
• [Journal Article] A pair of transmembrane receptors essential for the retention and pigmentation of hair (2012)
  • Author(s): Han R, Beppu H, Lee YK, Georgopoulos K, Larue L, Li E, Weiner L, Brissette JL
  • Journal Title: Genesis. Volume: Nov;50(11) Pages: 783-800
  • DOI: DOI:10.1002/dvg.22039
  • Peer Reviewed
• [Journal Article] BMPR-II is dispensable for formation of the limb skeleton (2011)
  • Author(s): Gamer LW, Tsuji K, Cox K, Capelo LP, Lowery J, Beppu H, Rosen V
  • Journal Title: Genesis Volume: 49(9) Pages: 719-24
  • DOI: DOI:10.1002/dvg.20761
  • Peer Reviewed
• [Presentation] BMPR2欠損線維芽細胞における亢進したTNF刺激反応性とNF-kB活性化 (2012)
  • Author(s): 別府秀幸
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] Augmented NF-kB signaling in BMPR2 deficient cells as the model for juvenile polyposis syndrome (2012)
  • Author(s): Beppu H
  • Organizer: TGF-beta meeting
  • Place of Presentation: Leiden Medical Center (The Netherlands)
  • Year and Date: 20120829-31
• [Presentation] BMPR2変異マウスにおける肺血管異常とその細胞内シグナル伝達異常 (2012)
  • Author(s): 別府秀幸
  • Organizer: PHサミット2012(招待講演)
  • Place of Presentation: 岡山
  • Year and Date: 20120728-29
• [Presentation] BMPR2-deficient fibroblast cells exhibit augmented NF-kB signaling in response to TNF-alpha (2012)
  • Author(s): Beppu H
  • Organizer: The 1st International Symposium by JSPS Core-to-Core Program (招待講演)
  • Place of Presentation: Tokyo (Japan)
  • Year and Date: 2012-01-24
• [Presentation] BMPR2-deficient fibroblast cells promote proliferation of epithelial cells in a cell culture system (2011)
  • Author(s): Beppu H
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: Barga (Italy)
  • Year and Date: 20110821-26