Regulation of hair growth and development by Wnt signaling pathway

• Project/Area Number: 16K10133
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nara Medical University
• Principal Investigator: Ouji Yukiteru 奈良県立医科大学, 医学部, 准教授 (50343421)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 発毛 / Wnt / 細胞 / 培養 / 移植 / 幹細胞 / 毛乳頭 / マウス / 毛乳頭細胞 / Wntシグナル / 上皮細胞 / 再生医学 / 毛包 / 発毛再生 / 細胞培養

Outline of Final Research Achievements

In order to control the growth and development of hair, it is necessary to identify the key factors and analyze their roles on trichogenesis. In the present study, I focused on Wnts and examined their expression in the hair growth stages and effects on the hair development using mouse follicle epithelial stem cells (EpSCs), dermal papilla cells (DPCs), isolated hair follicle organs and dorsal skin tissues. Various Wnts and Wnt-related molecules were found to be expressed apparently in complicated manners in the skin at each stage of hair development. Furthermore, some Wnts showed different effects of cell proliferation and gene expressions in cells, organs, and tissues. More precise expression analysis of the differences among Wnts was considered to lead to the identification of specifically important Wnt(s) in the respective stages of hair development and the control of trichogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究は、発毛現象に重要と考えられているWntシグナルに焦点を絞り、その発現を変化させ、発毛を制御するというコンセプトである。これは、従来の発毛研究（育毛剤開発・植毛等）とは全く異なり、分子レベルで発毛を制御するという特色があり、学術的には発毛メカニズムの解明し、社会的には脱毛治療薬の開発に寄与できると考えられる。

Research Products

• [Journal Article] Differentiation of embryonic stem cells into inner ear vestibular hair cells using vestibular cell derived-conditioned medium (2019)
  • Author(s): Sakagami M, Ouji Y, Kawai N, Misu M, Yoshikawa M, Kitahara T.
  • Journal Title: Biochem Biophys Rep. Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Effect of covering with cross-linked gelatin glue on tissue regeneration in a rat lung injury model. (2019)
  • Author(s): Kawai N, Suzuki S, Ouji Y, Takeda M, Sakagami M, Tojo T, Sawabata N, Yoshikawa M, Ikada Y, Taniguchi S.
  • Journal Title: Interact Cardiovasc Thorac Surg. Volume: ivy297 Issue: 1 Pages: 1-7
  • DOI: 10.1093/icvts/ivy297
  • Peer Reviewed
• [Journal Article] Induction of lung-like cells from mouse embryonic stem cells by decellularized lung matrix. (2018)
  • Author(s): Kawai N, Ouji Y, Sakagami M, Tojo T, Sawabata N, Yoshikawa M, Taniguchi S.
  • Journal Title: Biochem Biophys Rep. Volume: 15 Pages: 733-738
  • DOI: 10.1016/j.bbrep.2018.06.005
  • Peer Reviewed / Open Access
• [Journal Article] 脊髄炎で発症したトキソカラ症の1例 (2018)
  • Author(s): 井口直彦、桐山敬生、平位暢康、王寺幸輝、形岡博史、杉江和馬、吉川正英
  • Journal Title: Clinical Parasitology Volume: 29 Pages: 86-88
  • Peer Reviewed
• [Journal Article] 消化管に一隻のイヌ鉤虫が発見された日本在住のブラジル人症例 (2018)
  • Author(s): 赤松尚明、吉川正英、山田稔、楊孝治、平位暢康、王寺幸輝、有薗直樹
  • Journal Title: Clinical Parasitology Volume: 29 Pages: 75-79
  • Peer Reviewed
• [Journal Article] Ancylostoma ceylanicum, novel etiological agent for traveler's diarrhea-report of four Japanese patients who returned from Southeast Asia and Papua New Guinea. (2018)
  • Author(s): Yoshikawa M, Ouji Y, Hirai N, Nakamura-Uchiyama F, Yamada M, Arizono N, Akamatsu N, Yoh T, Kaya D, Nakatani T, Kikuchi E, Katanami Y, Satoh K, Maki R, Miyazato Y, Oba Y, Kasahara K, Mikasa K.
  • Journal Title: Trop Med Health Volume: 46 Issue: 1 Pages: 1-8
  • DOI: 10.1186/s41182-018-0087-8
  • Peer Reviewed
• [Journal Article] Efficient induction of inner ear hair cell-like cells from mouse ES cells using combination of Math1 transfection and conditioned medium from ST2 stromal cells. (2017)
  • Author(s): Ouji Y, Sakagami M, Omori H, Higashiyama S, Kawai N, Kitahara T, Wanaka A, Yoshikawa M.
  • Journal Title: Stem Cell Research Volume: 23 Pages: 50-56
  • DOI: 10.1016/j.scr.2017.06.013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] パプアニューギニアで感染し虫卵の遺伝子学的同定によりセイロン鉤虫症と診断した1例 (2017)
  • Author(s): 片浪 雄一、中村 ふくみ[内山]、佐藤公俊、王寺幸輝、吉川正英、三笠桂一
  • Journal Title: 感染症学雑誌 Volume: 91 Pages: 759-763
  • NAID: 130007728096
  • Peer Reviewed
• [Journal Article] 2009年にマレーシアにて感染したセイロン鉤虫症例 海外渡航にて感染した日本人の同症第1確定例 (2017)
  • Author(s): 山田稔、有薗直樹、赤松尚明、楊孝治、王寺幸輝、平位暢康、笠原敬、三笠桂一、吉川正英
  • Journal Title: Clinical Parasitology Volume: 28 Pages: 36-38
  • Peer Reviewed
• [Journal Article] 奈良県立医科大学感染症センター寄生虫外来10年の経験 海外渡航者外来とともに (2017)
  • Author(s): 平位暢康、吉川正英、小川拓、中村ふくみ、王寺幸輝、平田一記、今井雄一郎、藤倉裕之、吉井誠也、吉原真吾、今北菜津子、小川吉彦、米川真輔、菱矢直邦、梶田明裕、白石直敬、佐藤公俊、福森達也、辻本和徳、中川智代、宇野健司、笠原敬、前田光一、古西満、武山雅博、大西智子、片浪雄一、忽那賢志、三笠桂一
  • Journal Title: Clinical Parasitology Volume: 28 Pages: 9-12
  • Peer Reviewed
• [Journal Article] Antitumor effects of minodronate, a third-generation nitrogen-containing bisphosphonate, in synergy with γδT cells in human glioblastoma in vitro and in vivo. (2016)
  • Author(s): Nakazawa T, Nakamura M, Matsuda R, Nishimura F, Park YS, Motoyama Y, Hironaka Y, Nakagawa I, Yokota H, Yamada S, Tamura K, Takeshima Y, Omoto K, Tanaka Y, Ouji Y, Yoshikawa M, Tsujimura T, Nakase H.
  • Journal Title: J Neurooncol Volume: 129 Issue: 2 Pages: 231-241
  • DOI: 10.1007/s11060-016-2186-x
  • Peer Reviewed / Open Access
• [Journal Article] Development of Delayed Hemolytic Anemia After Treatment with Oral Artemether-Lumefantrine in Two Patients with Severe Falciparum Malaria. (2016)
  • Author(s): Tsuchido Y, Nakamura-Uchiyama F, Toyoda K, Iwagami M, Tochitani K, Shinohara K, Hishiya N, Ogawa T, Uno K, Kasahara K, Ouji Y, Kano S, Mikasa K, Shimizu T, Yoshikawa M, Maruyama H.
  • Journal Title: Am J Trop Med Hyg Volume: 96 Issue: 5 Pages: 1185-1189
  • DOI: 10.4269/ajtmh.16-0460
  • Peer Reviewed
• [Journal Article] Ancylostoma ceylanicum hookworm infection in Japanese traveler who presented chronic diarrhea after return from Lao People's Democratic Republic. (2016)
  • Author(s): Kaya D, Yoshikawa M, Nakatani T, Tomo-Oka F, Fujimoto Y, Ishida K, Fujinaga Y, Aihara Y, Nagamatsu S, Matsuo E, Tokoro M, Ouji Y, Kikuchi E.
  • Journal Title: Parasitol Int. Volume: 65 Issue: 6 Pages: 737-740
  • DOI: 10.1016/j.parint.2016.07.001
  • Peer Reviewed
• [Presentation] 卵形嚢由来細胞を用いたES細胞から内耳前庭有毛細胞への分化誘導法の開発 (2019)
  • Author(s): 阪上雅治、王寺幸輝、河合紀和、吉川正英、北原糺
  • Organizer: 第19回 日本再生医療学会総会
• [Presentation] Characterization of murine hair follicle stem cells under long-term culture conditions (2018)
  • Author(s): Ouji Y, Kawai N, Sakagami M, Yoshikawa M.
  • Organizer: 16th International Society for Stem Cell Research Annual Meeting
  • Int'l Joint Research
• [Presentation] Differentiation of mouse embryonic stem cells into inner ear cell-like cells using vestibular cell-conditioned medium. (2018)
  • Author(s): Sakagami M, Ouji Y, Kawai N, Kitahara T, Yoshikawa M.
  • Organizer: 16th International Society for Stem Cell Research Annual Meeting
  • Int'l Joint Research
• [Presentation] 脊髄炎で発症したトキソカラ症の1例 (2018)
  • Author(s): 井口直彦、桐山敬生、平位暢康、王寺幸輝、形岡博史、杉江和馬、吉川正英
  • Organizer: 第29回 日本臨床寄生虫学会大会
• [Presentation] 消化管に一隻のイヌ鉤虫が発見された日本在住のブラジル人症例 (2018)
  • Author(s): 赤松尚明、吉川正英、山田稔、楊孝治、平位暢康、王寺幸輝、有薗直樹
  • Organizer: 第29回 日本臨床寄生虫学会大会
• [Presentation] 長期培養維持した毛包上皮幹細胞のキャラクタリゼーション (2018)
  • Author(s): 王寺幸輝、河合紀和、阪上雅治、吉川正英
  • Organizer: 第17回 日本再生医療学会総会
• [Presentation] Effects of vestibular cell-conditioned medium on differentiation of embryonic stem cells into inner ear vestibular hair cells (2018)
  • Author(s): Sakagami M, Ouji Y, Kawai N, Kitahara T, Yoshikawa M.
  • Organizer: 41st Annual MidWinter Meeting, Association for research in otolaryngology (ARO)
  • Int'l Joint Research
• [Presentation] 皮膚上皮幹細胞の長期培養条件の検討とWntシグナル (2017)
  • Author(s): 王寺幸輝、河合紀和、阪上雅治、三須政康、吉川正英
  • Organizer: 第16回 日本再生医療学会総会
  • Place of Presentation: 仙台国際線センター（仙台市）
  • Year and Date: 2017-03-07
• [Presentation] 無細胞化マトリックスを用いたES細胞から肺細胞への効率的分化誘導法の開発 (2017)
  • Author(s): 河合紀和、王寺幸輝、阪上雅治、東条尚、谷口繁樹、吉川正英
  • Organizer: 第16回 日本再生医療学会総会
  • Place of Presentation: 仙台国際線センター（仙台市）
  • Year and Date: 2017-03-07
• [Presentation] ES細胞から分化誘導した内耳有毛細胞のキャラクタリゼーション (2017)
  • Author(s): 阪上雅治、王寺幸輝、河合紀和、北原糺、吉川正英
  • Organizer: 第16回 日本再生医療学会総会
  • Place of Presentation: 仙台国際線センター（仙台市）
  • Year and Date: 2017-03-07
• [Presentation] Maintenance and long-term expansion of murine skin epithelial stem cells by Wnt signaling pathway (2017)
  • Author(s): Ouji Y, Sakagami M, Kawai N, Yoshikawa M.
  • Organizer: 10th World Congress for Hair Research 2017
  • Int'l Joint Research
• [Presentation] セイロン鉤虫症は海外渡航時に注意すべき感染症であるー日本人4症例の検討ー (2017)
  • Author(s): 吉川正英、王寺幸輝、中村ー内山ふくみ、有薗直樹、山田稔、赤松尚明、賀屋大介、片浪雄一、眞木良祐、大場雄一郎
  • Organizer: 第58回 日本熱帯医学会大会
• [Presentation] 2009年にマレーシアにて感染したセイロン鉤虫症例 海外感染した日本人の同症第一確定例 (2017)
  • Author(s): 赤松尚明、山田稔、有薗直樹、楊孝治、王寺幸輝、吉川正英
  • Organizer: 第28回 日本臨床寄生虫学会大会
• [Presentation] 奈良医大感染症センター寄生虫専門外来10年の経験 (2017)
  • Author(s): 平位暢康、吉川正英、中村ふくみ、王寺幸輝、今井雄一郎、藤倉裕之、吉井誠也、吉原真吾、今北菜津子、小川拓、小川吉彦、米川真輔、平田一記、菱矢直邦、梶田明裕、白石直敬、佐藤公俊、福森達也、辻本和徳、中川智代、宇野健司、笠原敬、前田光一、古西満、武山雅博、大西智子、片浪雄一、忽那賢志、三笠桂一
  • Organizer: 第28回 日本臨床寄生虫学会大会
• [Presentation] 過去25年間に日本で報告された顎口虫症の原因虫種による臨床的特徴の比較 (2016)
  • Author(s): 上田和也、中村（内山）ふくみ、王寺幸輝、吉川正英
  • Organizer: 第27回 日本臨床寄生虫学会
  • Place of Presentation: しいのき迎賓館（金沢市）
• [Presentation] 旅行者セイロン鉤虫症の1例 (2016)
  • Author(s): 賀屋大介、中谷敏也、友岡文優、藤本優樹、石田光志、藤永幸久、相原洋祐、永松晋作、松尾英城、菊池英亮、王寺幸輝、所正治、吉川正英
  • Organizer: 第27回 日本臨床寄生虫学会
  • Place of Presentation: しいのき迎賓館（金沢市）
• [Book] 小児科、小児寄生虫感染症の対策・予防 (2018)
  • Author(s): 吉川正英、沢田敦、間瀬史絵、平位暢康、大西智子、武山雅博、笠原敬、王寺幸輝
  • Total Pages: 14
  • Publisher: 金原出版
• [Book] 日常検査で役立つ寄生虫・原虫検出法 抗原・抗体反応を利用した寄生虫検査 (2017)
  • Author(s): 王寺幸輝、吉川正英
  • Total Pages: 6
  • Publisher: Medical Technology
• [Book] Maintenance of Dermal Papilla Cells by Wnt-10b In Vitro. (2016)
  • Author(s): Ouji Y, Yoshikawa M.
  • Total Pages: 9
  • Publisher: Methods Mol Biol
• [Book] Maintenance of Skin Epithelial Stem Cells by Wnt-3a In Vitro. (2016)
  • Author(s): Ouji Y, Yoshikawa M.
  • Total Pages: 10
  • Publisher: Methods Mol Biol
• [Book] Induction of Inner Ear Hair Cells from Mouse Embryonic Stem Cells In Vitro. (2016)
  • Author(s): Yoshikawa M, Ouji Y.
  • Total Pages: 11
  • Publisher: Methods Mol Biol