Regeneration of Elastic Fiber

• Project/Area Number: 26670147
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kansai Medical University
• Principal Investigator: NAKAMURA Tomoyuki 関西医科大学, 医学部, 教授 (20362527)
• Co-Investigator(Renkei-kenkyūsha): KAGESHIMA Masami 関西医科大学, 医学部, 教授 (90251355) ; KUSUMOTO Kenji 関西医科大学, 医学部, 教授 (20161630)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 細胞外マトリックス / 弾性線維

Outline of Final Research Achievements

Elastic fiber is an extracellular matrix component that plays a key role in tissue elasticity. Degradation of elastic fibers directly causes skin looseness, emphysema, and arteriosclerosis. The turnover rate of elastic fiber is extremely slow, and there have been no method to regenerate elastic fibers so far. We have identified several proteins that play crucial roles in elastogenesis, and notably one of them could induce elastogenesis in cell culture. In this study, we engineered an assay system to measure mechanical characteristics of the extracellular matrix produced by cultured cells in order to analyze how elatogenic factors affect the elasticity of the matrix, with the goal of finding optimal condition for elastic fiber regeneration.

Research Products

• [Journal Article] The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis. (2015)
  • Author(s): Nakasaki M, Hwang Y, Xie Y, Kataria S, Gund R, Hajam EY, Samuel R, George R, Danda D, M J P, Nakamura T, Shen Z, Briggs S, Varghese S, Jamora C
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 8574-8574
  • DOI: 10.1038/ncomms9574
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice. (2015)
  • Author(s): Noda K, Nakamura T, Komatsu Y
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 466 Issue: 3 Pages: 585-591
  • DOI: 10.1016/j.bbrc.2015.09.089
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Regeneration of elastic fibers by three-dimensional culture on a collagen scaffold and the addition of latent TGF-β binding protein 4 to improve elastic matrix deposition. (2015)
  • Author(s): Aya R, Ishiko T, Noda K, Yamawaki S, Sakamoto Y, Tomihata K, Katayama Y, Yoshikawa K, Kubota H, Nakamura T, Naitoh M, Suzuki S
  • Journal Title: Biomaterials Volume: 72 Pages: 29-37
  • DOI: 10.1016/j.biomaterials.2015.08.036
  • NAID: 120005753831
  • Peer Reviewed / Open Access
• [Journal Article] Host stromal versican is essential for cancer-associated fibroblast function to inhibit cancer growth. (2015)
  • Author(s): Fanhchaksai K, Okada F, Nagai N, Pothacharoen P, Kongtawelert P, Hatano S, Makino S, Nakamura T and Watanabe H
  • Journal Title: International Journal of Cancer Volume: 138 Issue: 3 Pages: 630-641
  • DOI: 10.1002/ijc.29804
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Modeling autosomal recessive cutis laxa type 1C (ARCL1C) in mice reveals distinct functions of Ltbp-4 isoforms. (2015)
  • Author(s): Bultmann-Mellin I, Conradi A, Maul AC, Dinger K, Wempe F, Wohl AP, Imhof T, Wunderlich FT, Bunck AC, Nakamura T, Koli K, Bloch W, Ghanem A, Heinz A, von Melchner H, Sengle G, Sterner-Kock A
  • Journal Title: Disease Models and Mechanisms Volume: 8 Pages: 403-415
  • DOI: 10.1242/dmm.018960
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Exploring the origin and limitations of kidney regeneration. (2015)
  • Author(s): Endo T, Nakamura J, Sato Y, Asada M, Yamada R, Takase M, Takaori K, Oguchi A, Iguchi T, Higashi AY, Ohbayashi T, Nakamura T, Muso E, Kimura T, Yanagita M.
  • Journal Title: J Pathol. Volume: 236(2) Issue: 2 Pages: 251-63
  • DOI: 10.1002/path.4514
  • Peer Reviewed
• [Journal Article] Latent TGFβ binding protein-2 is essential for the development of ciliary zonule microfibrils. (2014)
  • Author(s): Inoue T., Ohbayashi T., Fujikawa Y., Yoshida H., Akama T.O., Noda K., Horiguchi M., Kameyama K., Hata Y., Takahashi K., Kusumoto K. and Nakamura T.
  • Journal Title: Human Molecular Genetics Volume: 23 Issue: 21 Pages: 5672-5682
  • DOI: 10.1093/hmg/ddu283
  • Peer Reviewed / Open Access
• [Journal Article] Prostaglandin E2 Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling. (2014)
  • Author(s): Yokoyama U, Minamisawa S, Sh ioda A, Ishiwata R, Jin MH, Masuda M, Asou T, Sugimoto Y, Aoki II, Nakamura T, and Ishikawa Y
  • Journal Title: Circulation. Volume: 129 Issue: 4 Pages: 487-496
  • DOI: 10.1161/circulationaha.113.004726
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo. (2014)
  • Author(s): Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Nakazeki F, Ide Y, Koyama S, Sowa N, Yahagi N, Shimano H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 5312-5312
  • DOI: 10.1038/srep05312
  • Peer Reviewed / Open Access
• [Journal Article] 弾性線維形成に必須のLTBP-4の役割 (2014)
  • Author(s): 中邨智之
  • Journal Title: 生化学 Volume: 86 Pages: 770-773
  • NAID: 40020314156
• [Presentation] TGFβに依存しないLTBPsの機能 (2015)
  • Author(s): 中邨智之
  • Organizer: 日本エラスチン研究会
  • Place of Presentation: アルカディア市ヶ谷、東京都
  • Year and Date: 2015-12-04
• [Presentation] 弾性線維形成因子が関与する多臓器疾患 (2015)
  • Author(s): 中邨智之
  • Organizer: 第35回日本サルコイドーシス／肉芽腫性疾患学会総会
  • Place of Presentation: ホテルエルセラーン大阪、大阪市
  • Year and Date: 2015-11-07
  • Invited
• [Presentation] TGFβ-independent role of LTBPs in microfibril and elastic fiber assembly, and molecular function of Fibulin-4. (2015)
  • Author(s): Tomoyuki Nakamura
  • Organizer: Gordon Research Conference on Elastin and Elastic Fiber
  • Place of Presentation: University of New England、米国Biddeford市、メイン州
  • Year and Date: 2015-07-26
  • Int'l Joint Research / Invited
• [Presentation] 動脈の硬さを規定する細胞外マトリックス (2015)
  • Author(s): 中邨智之
  • Organizer: 第47回日本動脈硬化学会学術集会
  • Place of Presentation: 仙台国際センター、仙台市
  • Year and Date: 2015-07-09
  • Invited
• [Presentation] LTBP-2とLTBP-4は弾性線維形成において重複する機能を有する (2015)
  • Author(s): 吉田秀之、藤川雄介、井上唯史、赤間智也、中邨智之
  • Organizer: 第４７回日本結合組織学会学術集会
  • Place of Presentation: コクヨホール、東京都
  • Year and Date: 2015-05-15
• [Presentation] 動脈弾性板形成の分子機構 (2014)
  • Author(s): 中邨智之
  • Organizer: 第51回血管研究会
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2014-10-30
  • Invited
• [Presentation] 生体の伸縮性を生み出すしくみ ～弾性線維の形成と再生の分子機構～ (2014)
  • Author(s): 中邨智之
  • Organizer: 第65回日本皮膚科学会中部支部学術大会
  • Place of Presentation: 大阪ナレッジキャピタルコングレコンベンションセンター
  • Year and Date: 2014-10-25
  • Invited
• [Presentation] 弾性線維の形成と再生の分子機構 (2014)
  • Author(s): 中邨智之
  • Organizer: 佐島シンポジウム
  • Place of Presentation: 京都大学
  • Year and Date: 2014-10-10
  • Invited