Aberrant epidermal expression of semaphorin 3A in pruritic skin diseases and development of new therapeutic drugs for pruritus

• Project/Area Number: 22591247
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Yokohama City University
• Principal Investigator: AIHARA Michiko 横浜市立大学, 医学研究科, 教授 (90231753)
• Co-Investigator(Kenkyū-buntansha): GOSHIMA Yoshio 横浜市立大学, 医学研究科, 教授 (00153750) ; NAGASHIMA Yoji 横浜市立大学, 医学研究科, 准教授 (10217995) ; 池澤 善郎 横浜市立大学, 医学研究科, 教授 (90046128)
• Co-Investigator(Renkei-kenkyūsha): IKEZAWA Zenro 国際医療福祉大学, 大学病院, 教授 (90046128) ; NAKAMURA Humio 横浜市立大学, 医学部, 准教授 (10262023)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 皮膚免疫 / 炎症学 / セマフォリン3A / アトピー性皮膚炎 / かゆみ / 乾癬 / コラーゲントリペプチド / C-ファイバー / 治療 / アレルギー性鼻炎 / シクロスポリン

Research Abstract

Semaphorin-3A (Sema3A) expression was lower in pruritic skin disorders compared with the healthy samples, whereas nerve growth factor (NGF) expression was higher. Intranasal administration of recombinant Sema3A in the allergic rhinitis model mice alleviated symptoms. Oral administration of collagen tripeptide in dry skin model mice suppressed scratching behavior and corrected Sema3A and NGF balance. In conclusion, we propose that administration and induction of Sema3A expression may useful to control the outgrowth of C-fibres, leading to pruritus, as a new therapeutic strategy for pruritic disorders.

Research Products

• [Journal Article] Interleukin-37 is elevated in subjects with atopic dermatitis. (2013)
  • Author(s): Fujita H, Inoue Y, Seto K, Komitsu N, Aihara M
  • Journal Title: J Dermatol Sci Volume: 69 Issue: 2 Pages: 173-176
  • DOI: 10.1016/j.jdermsci.2012.11.001
  • Peer Reviewed
• [Journal Article] Aberrant epidermal expression of semaphorin 3A and nerve growth factor in prurigo nodularis (2013)
  • Author(s): Takada S, Kou K, Nagashima Y,Ikezawa Z, Aihara M
  • Journal Title: Journal of Dermatology Volume: 40(in press) Issue: 5 Pages: 404-406
  • DOI: 10.1111/1346-8138.12085
  • Peer Reviewed
• [Journal Article] セマフォリンを用いたアトピー性皮膚炎治療の可能性 (2013)
  • Author(s): 五嶋良郎, 相原道子
  • Journal Title: 実験医学 Volume: 31(4) Pages: 488-494
  • URL: https://www.yodosha.co.jp/jikkenigaku/book/9784758100939/
• [Journal Article] セマフォリンを用いたアトピー性皮膚炎治療の可能性 (2013)
  • Author(s): 五嶋良郎,
  • Journal Title: 実験医学 Volume: 31 Pages: 448-494
• [Journal Article] Decreased Expression of Semaphorin-3A, a Neurite-Collapsing Factor, is Associated With Itch in PsoriaticSkin. (2012)
  • Author(s): Kou K, Nakamura F,Aihara M, Chen H, Seto K, Komori-Yamaguchi J, Kambara T, Nagashima Y,Goshima Y, Ikezawa Z
  • Journal Title: Acta Derm Venereol Volume: 92 Issue: 5 Pages: 521-528
  • DOI: 10.2340/00015555-1350
  • Peer Reviewed
• [Journal Article] Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model (2012)
  • Author(s): Okawa T, Yamaguchi Y, Takada S, Sakai Y, Numata N, Nakamura F,Nagashima Y,Ikezawa Z, Aihara M
  • Journal Title: JDermatol Sci Volume: 66(2) Issue: 2 Pages: 136-43
  • DOI: 10.1016/j.jdermsci.2012.02.004
  • Peer Reviewed
• [Journal Article] Intranasal Administration of Semaphorin-3A Alleviates Sneezing and Nasal Rubbing in a Murine Model of Allergic Rhinitis (2011)
  • Author(s): Sawaki H, Nakamura F,Aihara M, Nagashima Y,Komori-Yamaguchi J, Yamashita N, Nakagawara M, Goshoma Y, Ikezawa Z
  • Journal Title: Journal of Pharmacological Sciences Volume: 117 Issue: 1 Pages: 34-44
  • DOI: 10.1254/jphs.11005FP
  • NAID: 10029895884
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed
• [Journal Article] Role of Staphyococcus aureus, Interleukin-18, Nerve Growth Factor and Semaphorin 3A, an Axon Guidance Molecule, in Pathogenesis and Treatment of Atopic Dermatitis (2011)
  • Author(s): Ikezawa Z, Komori J, Ikezawa Y, Inoue Y, Kirino M, Katsuyama M, Aihara M
  • Journal Title: Allergy Asthma Immunol Res. Volume: 38 Pages: 246-254
• [Journal Article] Interleukin-18 is elevated in the horny layer in atopic dermatitis patients and associated with Staphylococcus aureus colonisation (2011)
  • Author(s): Inoue Y, Aihara M, Kirino M, Harada I, Komori-Yamaguchi J, Yamaguchi Y, Nagashima Y, Ikezawa Z
  • Journal Title: Br J Dermatol Volume: 164 Pages: 560-567
  • Peer Reviewed
• [Journal Article] A Role of Staphyococcus aureus, Interleukin-18, Nerve Growth Factor and Semaphorin 3A, an Axon Guidance Molecule, in Pathogenesis and Treatment of Atopic Dermatitis (2010)
  • Author(s): Ikezawa Z, Komori J, Ikezawa Y, Inoue Y, Kirino M, Katsuyama M, Aihara M
  • Journal Title: Allergy, Asthma & Immunology Research Volume: 2 Issue: 4 Pages: 235-246
  • DOI: 10.4168/aair.2010.2.4.235
  • Peer Reviewed
• [Presentation] Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model (2012)
  • Author(s): Okawa T, Yamaguchi Y, Takada S, Sakai Y, Numata N, Nakamura F, Nagashima Y,Ikezawa Z, Aihara M
  • Organizer: The 37th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Loisir Hotel &Spa Tower Nara Pacific Hotel(Okinawa)
  • Year and Date: 2012-12-08
• [Presentation] Oral administration of collagen trioeotide improves dryness and pruritus in the acetone-induced dry skin model (2012)
  • Author(s): Okawa T, Yamaguchi Y, Takada S, Sakai Y, Numata N, Nakamura F, Nagashima Y,Ikezawa Z, Aihara M
  • Organizer: 22nd International Symposium of Itch
  • Place of Presentation: Bellesalle jimbocho (Tokyo)
  • Year and Date: 2012-10-06
• [Presentation] ランチョンセミナー5 皮膚バリア機能が乳幼児アトピー性皮膚炎の発症におよぼす影響について (2012)
  • Author(s): 相原道子
  • Organizer: 第42回日本皮膚アレルギー・接触皮膚炎学会総会学術大会
  • Place of Presentation: 軽井沢プリンスホテルウエスト(長野県)
  • Year and Date: 2012-07-15
• [Presentation] Decreased Semaphorin-3A Expression in the Lesional Skin of Patients with Psoriasis Vulgaris. (2011)
  • Author(s): Kou K, Nakamura F,Aihara M, Chin H, Seto K, Takada S, Komori-yamaguchi J, Kambara T, Nagashima Y,Goshima Y, Ikezawa Z
  • Organizer: The 36th Annual Meeting of the Japanese Society for Investingative Dermatology
  • Place of Presentation: KyotoInternational Conference Center(Kyoto)
  • Year and Date: 2011-12-10
• [Presentation] Semaphorin3A expression is decreased in the epidermis of prurigo nodularis (2011)
  • Author(s): Takada S, Kou K,Nagashima Y,Ikezawa Z, Aihara M
  • Organizer: The 36th Annual Meeting of the Japanese Society for Investingative Dermatology
  • Place of Presentation: kyotoInternational Conference Center(Kyoto)
  • Year and Date: 2011-12-10
• [Presentation] Decreased Semaphorin-3A Expression in the Lesional Skin of Patients with Psoriasis Vulgaris (2011)
  • Author(s): Kou K, Nakamura F, Aihara M, Chin H, Seto K, Takada S, Komori-yamaguchi J, Kambara T, Nagashima Y, Goshima Y, Ikezawa Z
  • Organizer: The 36th Annual Meeting of the Japanese Society for Investingative Dermatology
  • Place of Presentation: Kyoto International Conference center (Kyoto, Japan)
  • Year and Date: 2011-12-10
• [Presentation] Semaphorin3A expression is decreased in the epidermis of prurigo nodularis (2011)
  • Author(s): Takada S, Kou K, Nagashima Y, Ikezawa Z, Aihara M
  • Organizer: The 36th Annual Meeting of the Japanese Society for Investingative Dermatology
  • Place of Presentation: Kyoto International Conference center(Kyoto, Japan)
  • Year and Date: 2011-12-10
• [Presentation] 痒みのメカニズムから考えるアトピー性皮膚炎の治療戦略 (2011)
  • Author(s): 相原道子
  • Organizer: 第75回日本皮膚科学会東部支部学術大会
  • Place of Presentation: ベイシア文化ホール(群馬県)
  • Year and Date: 2011-09-18
• [Presentation] 痒みのメカニズムから考えるアトピー性皮膚炎の治療戦略 (2011)
  • Author(s): 相原道子
  • Organizer: 第75回日本皮膚科学会東部支部学術大会
  • Place of Presentation: ベイシア文化ホール(群馬県前橋市)(招待講演)
  • Year and Date: 2011-09-18
• [Presentation] アトピー性皮膚炎難治化とその痒みの病態及び治療の展望 (2010)
  • Author(s): 池澤善郎
  • Organizer: 第60回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京,東京国際フォーラム(招待講演)
  • Year and Date: 2010-11-26
• [Presentation] 重症アトピー性皮膚炎患者におけるシクロスポリン内服療法の効果と血清IL-18変動の臨床的意義 (2010)
  • Author(s): 侯健全, 長島真由美, 大川智子, 守屋真希, 稲川紀章, 井上雄介, 野村有希, 蒲原毅, 相原道子, 池澤善郎
  • Organizer: 6th Tokyo scientific forum for Atopic Dermatitis and Psoriasis
  • Place of Presentation: 東京,大手町ファーストスクェア ウエストタワー23F
  • Year and Date: 2010-11-13
• [Presentation] Intranasal administration of Semaphorin3A alleviates murine allergic rhinitis (2010)
  • Author(s): Sawaki H, Nakamura F,Aihara M, Nagashima Y,Nakazawa M, Goshima Y, Ikezawa Z
  • Organizer: The 35th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: WakayamaPrefectual Cultural Hall(Wakayama)
  • Year and Date: 2010-10-30
• [Presentation] Decreased expression of semaphorin3A in the lesional skin of psoriasis vulgaris with itch. (2010)
  • Author(s): Kou K, Nakamura F,Aihara M, Seto K, Komori J, Kambara T, Nagashima Y,Goshima Y, Ikezawa Z
  • Organizer: 20th International Symposium ofItch
  • Place of Presentation: Tokyostation conference(Tokyo)
  • Year and Date: 2010-10-30
• [Presentation] Decreased expression of semaphorin3A in the lesional skin of psoriasis vulgaris with itch (2010)
  • Author(s): Kou K, Nakamura F, Aihara M, Seto K, Komori-Yamaguchi J, Kambara T, Nagashima Y, Goshima Y, Ikezawa Z
  • Organizer: 20th International Symposium of Itch
  • Place of Presentation: 東京,東京ステーションコンファレンス6F
  • Year and Date: 2010-10-30
• [Presentation] Intra nasal administration of Semaphorin3A alleviates marine allergic rhinitis (2010)
  • Author(s): Sawaki H, Nakamura F, Aihara M, Nagashima Y, Nakazawa M, Komori-Yamaguchi J, Goshima Y, Ikezawa Z
  • Organizer: 20th International Symposium of Itch
  • Place of Presentation: 東京,東京ステーションコンファレンス6F
  • Year and Date: 2010-10-30
• [Presentation] Semaphorin3Aの経鼻投与がOVA (2010)
  • Author(s): 澤城晴名, 中村史雄,相原道子, 長嶋洋治,池澤善郎, 五嶋良郎
  • Organizer: 第123回薬理学会関東部会
  • Place of Presentation: 自治医科大学地域医療情報研修センター(栃木県)
  • Year and Date: 2010-10-23
• [Presentation] Semaphorin3Aの経鼻投与がOVA誘発性アレルギー性鼻炎に及ぼす効果の検討 (2010)
  • Author(s): 澤城晴名, 中村史雄, 相原道子, 長嶋洋治, 池澤善郎, 五嶋良郎
  • Organizer: 第123回薬理学会関東部会
  • Place of Presentation: 栃木,自治医科大学地域医療情報研修センター
  • Year and Date: 2010-10-23
• [Presentation] 重症アトピー性皮膚炎に対するシクロスポリン内服療法の治療効果と患者満足度の検討 (2010)
  • Author(s): 侯健全, 長島真由美, 大川智子, 守屋真希, 稲川紀章, 野村有希, 蒲原毅, 相原道子, 池澤善郎
  • Organizer: 日本皮膚科学会第831回東京地方会
  • Place of Presentation: 東京,都市センターホテル
  • Year and Date: 2010-07-10
• [Presentation] Correlation between Semaphorin3A expression snd the itch intensity and severity in patients with psoriasis (2010)
  • Author(s): Kou K, Nakamura F,Aihara M, Seto K, Kanbara T, Nagashima Y,Goshima Y, Ikezawa Z
  • Organizer: 9th Meeting of the German-Japanese Society of Dermatology
  • Place of Presentation: LeonardoHotelWeimar(German)
  • Year and Date: 2010-06-10
• [Presentation] Interleukin-18 in horney layer of atopic dermatitis (AD) patients is associated with the severity. (2010)
  • Author(s): Inoue Y, Aihara M, Harada I, Komori J, Kirino M, Nagashima Y, Ikezawa Z
  • Organizer: 9th Meeting of the German-Japanese Society of Dermatology
  • Place of Presentation: Weimar,ドイツ
  • Year and Date: 2010-06-10
• [Presentation] Correlation between Semaphorin3A expression and the itch intensity and severity in patients with psoriasis (2010)
  • Author(s): Kou K, Nakamiura F, Aihara M, Seto K, Komori J, Kambara T, Nagashima Y., Goshma Y, Ikezawa Z
  • Organizer: 9th Meeting of the German-Japanese Society of Dermatology
  • Place of Presentation: Weimar,ドイツ
  • Year and Date: 2010-06-10
• [Presentation] A probable role of interleukin-18(IL-18) in pathogenesis of atopic dermatitis (AD) from the quantitative analysis of IL-18 in horny layer of AD patients. (2010)
  • Author(s): Ikezawa Z, Inoue Y, Aihara M, Harada I, Komori J, Kirino M, Nagashima Y
  • Organizer: 28th Symposium Collegium International Allergicum Translational Science
  • Place of Presentation: Ischia,イタリア(招待講演)
  • Year and Date: 2010-04-25
• [Presentation] Oral administration of collagen trioeotide improves dryness and pruritus in the acetone-induced dry skin model
  • Author(s): Okawa T
  • Organizer: 22nd International Symposium of Itch
  • Place of Presentation: ベルサール神保町（東京都）
• [Presentation] Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model
  • Author(s): Okawa T
  • Organizer: The 37th Annual Meeting of the Japanese Society for Investigative Dermatology,
  • Place of Presentation: Loisir Hotel & Spa Naha（沖縄県）
• [Presentation] セマフォリン3Aによる表皮内神経線維の制御とかゆみ治療の展望
  • Author(s): 侯 健全
  • Organizer: 第42回日本皮膚アレルギー・接触皮膚炎学会総会学術大会
  • Place of Presentation: 軽井沢プリンスホテル（長野県）
  • Invited