Roles of Notch signaling in regulating autophagy induction and stress response

• Project/Area Number: 17K10218
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kindai University
• Principal Investigator: Moriyama Mariko 近畿大学, 薬学総合研究所, 准教授 (40595295)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 創傷治癒 / Notchシグナル / 皮膚免疫 / 皮膚 / 乾癬 / ストレス応答 / アポトーシス / オートファジー / ストレス

Outline of Final Research Achievements

In this study, we have found a new role of Hes1 in the skin wound healing. Skin epidermal-specific knockout of Hes1 resulted in the delayed wound healing through regulating the skin immunity and inflammation. In addition, we found that the Hes1 was involved in the development of proriasis.

Academic Significance and Societal Importance of the Research Achievements

皮膚はからだの最表面に位置しているため、皮膚疾患は命を脅かすのみならず、見た目などの問題にも関わることから、QOLに大きな影響を与えることとなる。今回の研究成果により、Notchシグナルを制御することで褥瘡などの創傷治癒や乾癬などの治療に役立つことが期待される。さらに、皮膚免疫に関わるその他の疾患、例えばアトピー性皮膚炎や接触性皮膚炎などにも応用できる可能性を秘めている。

Research Products

• [Journal Article] Adipose-derived Stromal/Stem Cells Improve Epidermal Homeostasis (2019)
  • Author(s): Mariko Moriyama, Shunya Sahara, Kaori Zaiki, Ayumi Ueno, Koichi Nakaoji, Kazuhiko Hamada, Toshiyuki Ozawa, Daisuke Tsuruta, Takao Hayakawa, Hiroyuki Moriyama
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 18371-18371
  • DOI: 10.1038/s41598-019-54797-5
  • Peer Reviewed / Open Access
• [Journal Article] Role of FBXW7 in the quiescence of gefitinib-resistant lung cancer stem cells in EGFR-mutant non-small cell lung cancer (2019)
  • Author(s): Hidayat M, Mitsuishi Y, Takahashi F, Tajima K, Yae T, Miyahara K, Hayakawa D, Winardi W, Ihara H, Koinuma Y, Wirawan A, Nurwidya F, Kato M, Kobayashi I, Sasaki S, Takamochi K, Hayashi T, Suehara Y, Moriyama M, Moriyama H, Habu S, Takahashi K.
  • Journal Title: Bosnian Journal of Basic Medical Sciences Volume: 8;19(4) Pages: 355-367
  • DOI: 10.17305/bjbms.2019.4227
  • Peer Reviewed / Open Access
• [Journal Article] Notch signaling enhances stemness by regulating metabolic pathways through modifying p53, NF-κB, and HIF-1α. (2018)
  • Author(s): Moriyama H, Moriyama M, Ozawa T, Tsuruta D, Iguchi T, Tamada S, Nakatani T, Nakagawa K, Hayakawa T
  • Journal Title: Stem Cells Dev Volume: 印刷中 Issue: 13 Pages: 935-947
  • DOI: 10.1089/scd.2017.0260
  • Peer Reviewed / Open Access
• [Journal Article] BNIP3 upregulation via stimulation of ERK and JNK activity is required for the protection of keratinocytes from UVB-induced apoptosis. (2017)
  • Author(s): Moriyama M, Moriyama H, Uda J, Kubo H, Nakajima Y, Goto A, Morita T, Hayakawa T.
  • Journal Title: Cell Death Dis Volume: 8 Issue: 2 Pages: e2576-e2576
  • DOI: 10.1038/cddis.2017.4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Hes1の皮膚における新たな役割. (2020)
  • Author(s): 梅田大輔, 森山麻里子, 早川堯夫, 森山博由
  • Organizer: 日本薬学会第140年会
• [Presentation] FoxO3a Palys Roles in the Wound Healing by Regulating Mitochondrial Dynamics (2019)
  • Author(s): Mariko Moriyama
  • Organizer: Japan - Singapore International Skin Conference 2019
  • Int'l Joint Research
• [Presentation] Hes1の皮膚における新たな役割. (2019)
  • Author(s): 梅田大輔, 森山麻里子, 早川堯夫, 森山博由
  • Organizer: 第69回日本薬学会関西支部総会・大会
• [Presentation] Adipose-derived stromal/stem cells improve epidermal homeostasis (2019)
  • Author(s): Hiroki Kiriyama, Mariko Moriyama, Shunya Sahara, Kaori Zaiki, Ayumi Ueno, Koichi Nakaoji, Kazuhiko Hamada, Toshiyuki Ozawa, Daisuke Tsuruta, Takao Hayakawa, Hiroyuki Moriyama
  • Organizer: 44th Annual Meeting of the Japanese Society for Investigative Dermatology
• [Presentation] FoxO3a plays roles in the wound healing by regulating mitochondrial dynamics (2019)
  • Author(s): Mariko Moriyama, Takao Hayakawa, Hiroyuki Moriyama
  • Organizer: 44th Annual Meeting of the Japanese Society for Investigative Dermatology
• [Presentation] FoxO3a Plays Roles in the Wound Healing by Regulating Mitochondrial Dynamics (2019)
  • Author(s): Mariko Moriyama
  • Organizer: Japan - Singapore International Skin Conference 2019
  • Int'l Joint Research
• [Presentation] FoxO3a Plays Roles in the Wound Healing through Autophagy (2018)
  • Author(s): Takashi Morita, Mariko Moriyama, Takao Hayakawa, Hiroyuki Moriyama
  • Organizer: 16th International Society for Stem Cell Research 2018
  • Int'l Joint Research
• [Presentation] Crucial role of BNIP3-induced autophagy in differentiation and maintenance of skin epidermis (2018)
  • Author(s): Sonoka Fujinami, Mariko Moriyama, Takashi Morita, Ken Natsuga, Takao Hayakawa, Hiroyuki Moriyama
  • Organizer: 16th International Society for Stem Cell Research 2018
  • Int'l Joint Research
• [Presentation] 皮膚に於けるオートファジーの役割 (2018)
  • Author(s): 森山麻里子
  • Organizer: 5th 幹細胞・細胞分化リトリート
• [Presentation] FoxO3aによるオートファジーの誘導は皮膚の恒常性維持に重要である (2018)
  • Author(s): 藤波そのか, 森山麻里子, 森田貴士, 松本諭以子, 尾崎紀文, 和田晃拡, 早川堯夫, 森山博由
  • Organizer: 第67回日本薬学会近畿支部会
• [Presentation] FoxO3a plays roles in the wound healing through autophagy (2018)
  • Author(s): Takashi Morita, Mariko Moriyama, Yuka Nakajima, Arisa Goto, Ryo Morita, Ken Natsuga, Takao Hayakawa, Hiroyuki Moriyama
  • Organizer: 第41回日本分子生物学会総会
• [Presentation] オートファジー制御因子BNIP3は表皮恒常性の維持に寄与する (2018)
  • Author(s): 森田貴士、森山麻里子、早川堯夫、森山博由
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] BNIP3は紫外線から皮膚を保護するのに重要な役割を果たす (2018)
  • Author(s): 森田遼、森田貴士、森山麻里子、早川堯夫、森山博由
  • Organizer: 日本薬学会第138年会
• [Presentation] BNIP3-induced autophagy is required for maintenance of epidermal homeostasis. (2017)
  • Author(s): Yuki Marutani, Mariko Moriyama, Takashi Morita, Yuka Nakajima, Arisa Gotoh, Ryo Morita, Ken Natsuga, Takao Hayakawa, Hiroyuki Moriyama.
  • Organizer: 15th International Society for Stem Cell Research
  • Int'l Joint Research
• [Presentation] 皮膚に於けるオートファジーの役割 (2017)
  • Author(s): 森山麻里子、森山博由
  • Organizer: 幹細胞・細胞分化リトリート
• [Presentation] 皮膚におけるFoxo3aの役割 (2017)
  • Author(s): 丸谷祐樹、森山麻里子、森山博由
  • Organizer: 幹細胞・細胞分化リトリート
• [Presentation] BNIP3-induced Autophagy is Required for Maintenance of Epidermal Homeostasis (2017)
  • Author(s): Mariko Moriyama, Hiroyuki Moriyama, Takao Hayakawa
  • Organizer: 47th European Society for Dermatological Research
  • Int'l Joint Research
• [Presentation] 皮膚におけるFoxo3aの役割 (2017)
  • Author(s): 丸谷祐樹, 森山麻里子, 森田貴士, 後藤ありさ, 森田遼, 松本諭以子, 早川堯夫, 森山博由
  • Organizer: 第６７回日本薬学会近畿支部会
• [Presentation] オートファジー関連因BNIP3は表皮分化に重要な働きをする (2017)
  • Author(s): 森田貴士, 森山麻里子, 後藤ありさ, 森田遼, 丸谷祐樹, 松本諭以子, 宇田純輝, 夏賀 健, 早川堯夫, 森山博由
  • Organizer: 第６７回日本薬学会近畿支部会
• [Presentation] FoxO3a Plays Roles in the Wound Healing through Autophagy (2017)
  • Author(s): Takashi Morita, Mariko Moriyama, Yuka Nakajima, Arisa Goto, Ryo Morita, Ken Natsuga, Takao Hayakawa, Hiroyuki Moriyama
  • Organizer: The 40th Annual meeting of the Molecular biology society of Japan
• [Presentation] BNIP3 is required for the protection of keratinocytes from UVB-induced apoptosis through induction of autophagy (2017)
  • Author(s): Mariko Moriyama, Hirokazu Kubo, Yuka Nakajima, Arisa Goto,Takao Hayakawa, Hiroyuki Moriyama
  • Organizer: 42th Annual Meeting of the Japanese Society for Investigative Dermatology
• [Book] Bio Industry 2018年9月号 (2018)
  • Author(s): 森山麻里子, 赤木淳二, 北郡秀晃, 森山博由
  • Publisher: シーエムシー出版