A novel therapeutic strategy against psoriasis by using nicotinic acetylcholine receptor modulator, SLURP-1

• Project/Area Number: 15K21370
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology; Pharmacology in pharmacy
• Research Institution: Keio University
• Principal Investigator: Moriwaki Yasuhiro 慶應義塾大学, 薬学部(芝共立), 講師 (00392150)
• Research Collaborator: TSUJI Shoutaro
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 乾癬 / SLURP-1 / 黄色ブドウ球菌 / 抗菌活性 / 皮膚バリア機能 / 正常ヒト表皮角化細胞 / α7ニコチン性アセチルコリン受容体 / T-reg / IL-22

Outline of Final Research Achievements

SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder　characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Recently, SLURP1-deficient mice show MDM-like symptoms such as severe palmoplantar keratoderma characterized by increased keratinocyte proliferation and water barrier defects. Although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied. In our experiment, we found SLURP1 expression is greatly increased within the skin lesions in a psoriatic mouse model. In addition, recombinant SLURP1 suppressed the growth of S. aureus, which is associated with disease severity in psoriasis. These results suggest that SLURP1 may contribute to the pathogenesis of psoriasis.

Research Products

• [Journal Article] HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. (2017)
  • Author(s): Shoutaro Tsuji, Kota Washimi, Taihei Kageyama, Makiko Yamashita, Rieko Matsuura, Tomoyuki Yokose, Yoichi Kameda, Hiroyuki Hayashi, Takao Morohoshi, Yukio Tsuura, Toshikazu Yusa, Takashi Sato, Hisashi Narimatsu, Yasuhiro Moriwaki, Hidemi Misawa, Kenzo Hiroshima, Yohei Miyagi, and Kohzoh Imai, et al.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 45768-45768
  • DOI: 10.1038/srep45768
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A bis-malonic acid fullerene derivative significantly suppressed IL-33-induced IL-6 expression by inhibiting NF-kappaB activation (2016)
  • Author(s): Funakoshi-Tago M, Miyagawa Y, Ueda F, Mashino T, Moriwaki Y, Tago K, Kasahara T, Tamura H
  • Journal Title: Int Immunopharmacol Volume: 40 Pages: 254-264
  • DOI: 10.1016/j.intimp.2016.08.031
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Reappraisal of VAChT-Cre: Preference in slow motor neurons innervating type I or IIa muscle fibers (2016)
  • Author(s): Misawa H, Inomata D, Kikuchi M, Maruyama S, Moriwaki Y, Okuda T, Nukina N, Yamanaka T.
  • Journal Title: Genesis. Volume: 54 Issue: 11 Pages: 568-572
  • DOI: 10.1002/dvg.22979
  • Peer Reviewed
• [Journal Article] Selective expression of osteopontin in ALS-resistant motor neurons is a critical determinant of late phase neurodegeneration mediated by matrix metalloproteinase-9. (2016)
  • Author(s): Morisaki Y, Niikura M, Watanabe M, Onishi K, Tanabe S, Moriwaki Y, Okuda T, Ohara S, Murayama S, Takao M, Uchida S, Yamanaka K, *Misawa H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 27354-27354
  • DOI: 10.1038/srep27354
  • Peer Reviewed / Open Access
• [Journal Article] ニコチン受容体修飾因子SLURP-1による乾癬の新規治療戦略 (2016)
  • Author(s): 森脇康博
  • Journal Title: 臨床免疫・アレルギー科 Volume: 66 Pages: 45-49
• [Journal Article] IL-22/STAT3-induced increases in SLURP1 expression within psoriatic lesions exerts antimicrobial effects against Staphylococcus aureus. (2015)
  • Author(s): Moriwaki Y, Takada K, Nagasaki T, Kubo N, Ishii T, Kose K, Kageyama T, Tsuji S, Kawashima K, Misawa H
  • Journal Title: PLoS One Volume: 該当なし Issue: 10 Pages: e0140750-e0140750
  • DOI: 10.1371/journal.pone.0140750
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Transcriptional regulation of SLURP2, a psoriasis-associated gene, is under control of IL-22 in the skin: a special reference to the nested gene LYNX1. (2015)
  • Author(s): Moriwaki Y, Takada K, Tsuji S, Kawashima K, Misawa H
  • Journal Title: Int immunopharmacol Volume: 29 Issue: 1 Pages: 71-75
  • DOI: 10.1016/j.intimp.2015.05.030
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 中皮腫マーカー蛋白質, インテレクチン-1と1, 2-diolの結合様式の解析 (2017)
  • Author(s): 長崎俊憲, 森脇康博, 三澤日出巳, 辻祥太郎.
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール・長崎県長崎市
  • Year and Date: 2017-03-15
• [Presentation] Role for α7 nicotinic acetylcholine receptors in naive T cell differentiation into regulatory T cell. (2016)
  • Author(s): Kawashima K, Mashimo T, Fujii T, Moriwaki Y, Misawa H, Ono S.
  • Organizer: 46th Annual Meeting, Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-11-15
  • Int'l Joint Research