Investigation of the effect of Wnt signaling on salivary gland development.

• Project/Area Number: 26861547
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry
• Research Institution: Osaka University
• Principal Investigator: FUJII SHINSUKE 大阪大学, 医学(系)研究科(研究院), 特任助教(常勤) (60452786)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 唾液腺 / Wnt / 増殖 / 分化 / マウス / 発生 / Wntシグナル

Outline of Final Research Achievements

In this study, it was shown how Wnt signaling controls epithelial morphogenetic changes, such as growth and branching, and differentiation using the salivary gland as a model. When mesenchyme-free submandibular salivary gland (SMG) epithelium at E13 was cultured with IWP2, a Wnt secretion inhibitor, growth and branching of SMG were suppressed. Activation of Wnt/β-catenin signaling promoted proliferation of SMG duct progenitor cells which were positive for Ki67 staining. Experiments using genetically manipulated mice (Ctnnb1(Ex3)Δ/Δ ) revealed that the numbers of multiple acinar-like structures, defined by the existence of a central lumen, in Ctnnb1(Ex3)Δ/Δ mice were reduced compared with those of wild type mice. And protein levels of aquaporin 5, parotid secretory protein and phosphorylated AKT in Ctnnb1(Ex3)Δ/Δ mice were suppressed.

Research Products

• [Journal Article] Arl4c expression in colorectal and lung cancers promotes tumorigenesis and may represent a novel therapeutic target (2015)
  • Author(s): Fujii, S., Matsumoto, S., Nojima, S. Morii, E., and Kikuchi, A.
  • Journal Title: Oncogene Volume: In press Issue: 37 Pages: 4834-4844
  • DOI: 10.1038/onc.2014.402
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The P2Y2 receptor promotes Wnt3a and EGF-induced epithelial tubular formation of IEC6 cells by binding to integrins. (2015)
  • Author(s): Ibuka, S., Matsumoto, S., Fujii, S., Kikuchi, A.
  • Journal Title: J Cell Sci. Volume: 128(11) Issue: 11 Pages: 2156-2168
  • DOI: 10.1242/jcs.169060
  • Peer Reviewed
• [Journal Article] Effect of CTGF/CCN2 on osteo/cementoblastic and fibroblastic differentiation of a human periodontal ligament stem/progenitor cell line. (2015)
  • Author(s): Yuda A, Maeda H, Fujii S, Monnouchi S, Yamamoto N, Wada N, Koori K, Tomokiyo A, Hamano S, Hasegawa D, Akamine A
  • Journal Title: J Cell Physiol. Volume: 230 Issue: 1 Pages: 150-159
  • DOI: 10.1002/jcp.24693
  • Peer Reviewed
• [Journal Article] A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures. (2014)
  • Author(s): Matsumoto, S., Fujii, S., Sato, A., Ibuka, S., Kagawa, Y., Ishii, M., and Kikuchi, A.
  • Journal Title: EMBO J Volume: 33 Issue: 7 Pages: 702-718
  • DOI: 10.1002/embj.201386942
  • Peer Reviewed
• [Journal Article] The roles of calcium-sensing receptor and calcium channel in osteogenic differentiation of undifferentiated periodontal ligament cells. (2014)
  • Author(s): Koori K, Maeda H, Fujii S, Tomokiyo A, Kawachi G, Hasegawa D, Hamano S, Sugii H, Wada N, Akamine A.
  • Journal Title: Cell Tissue Res. Volume: 357 Issue: 3 Pages: 707-718
  • DOI: 10.1007/s00441-014-1918-5
  • Peer Reviewed
• [Journal Article] Semaphorin 3A induces mesenchymal stem-like properties in human periodontal ligament cells (2014)
  • Author(s): Wada N, Maeda H, Hasegawa D, Gronthos S, Bartold PM, Menicanin D, Fujii S, Yoshida S, Tomokiyo A, Monnouchi S, Akamine A
  • Journal Title: Stem Cells Dev Volume: (Epub ahead of print) Issue: 18 Pages: 2225-2236
  • DOI: 10.1089/scd.2013.0405
  • Peer Reviewed
• [Presentation] Arl4c expression is involved in tumorigenesis of colorectal cancer, lung adenocarcinoma and squamous cell carcinoma (2015)
  • Author(s): Shinsuke Fujii, Shinji Matsumoto, Akira Kikuchi.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2015-10-10
• [Presentation] Arl4c expression is involved in tumorigenesis of colorectal and lung cancers (2014)
  • Author(s): Shinsuke Fujii, Shinji Matsumoto, Akira Kikuchi.
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-27
• [Remarks] 大阪大学医学系研究科分子病態生化学
  • URL: http://www.med.osaka-u.ac.jp/pub/molbiobc/index.html
• [Remarks] 大阪大学医学系研究科 分子病態生化学
  • URL: http://www.med.osaka-u.ac.jp/pub/molbiobc/index.html
• [Patent(Industrial Property Rights)] Arl4c遺伝子の発現を抑制する物質又はタンパク質の活性を抑制する物質を含む、癌の治療の為の医薬組成物(核酸を含む) (2014)
  • Inventor(s): 菊池 章、松本 真司、藤井 慎介
  • Industrial Property Rights Holder: 菊池 章、松本 真司、藤井 慎介
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-05-13