Oxidative stress in the skin of a model of atopic dermatitis caused by skin barrier disfunction

• Project/Area Number: 23791271
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Kagawa University
• Principal Investigator: NAKAI Kozo 香川大学, 医学部附属病院, 助教 (40363204)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アトピー性皮膚炎 / 皮膚バリア機能 / フィラグリン / 酸化ストレス / ロリクリン / Klotho / 病態 / 治療 / 活性酸素 / フリーラジカル / 国際研究者交流 / 国際情報交流

Outline of Final Research Achievements

The deranged skin barrier function due to reduction of filaggrin expression in epidermis causes atopic dermatitis. We found that the expression of important skin barrier function factors is reduced in the skin of a mouse model of atopic dermatitis. N-acetylcysteine, an antioxidant, recovered the reduced expression of important skin barrier function factors. Moreover, topical application of N-acetylcysteine recovered the skin barrier function in human atopic dermatitis patients. These findings suggest that oxidative stress regulates the epidermal keratinization and skin barrier function.

Research Products

• [Journal Article] Phosphate-buffered saline induces filaggrin expression in a human epidermal keratinocyte cell line (HaCaT cells) (2015)
  • Author(s): Nakai K, Yoneda K, Nakagawa T, Moriue T, Kubota Y.
  • Journal Title: Dermatologica Sinica Volume: 0 Pages: 0-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] betaKlotho expression is reduced in human non-melanoma skin cancer (2015)
  • Author(s): Nakai K, Yoneda K, Moriue J, Moriue T, Koura A, Yokoi I, Ishikawa E, Yasuo K, Haba R, Kushida Y, Katsuki N, Inoue S
  • Journal Title: International Journal of Dermatology Volume: 0 Pages: 0-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of topical N-acetylcysteine on skin hydration/transepidermal water loss in healthy volunteers and atopic dermatitis patients (2015)
  • Author(s): Kozo Nakai, Kozo Yoneda, Yumi Murakami, Ayako Koura, Reiko Maeda, Asuka Tamai, Emiko Ishikawa, Ikumi Yokoi, Junko Moriue, Tetsuya Moriue, Yasuo Kubota
  • Journal Title: Annals of Dermatology Volume: 0 Pages: 0-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Two cases of nevus sebaceous accompanying secondary tumors with βKlotho expression. (2014)
  • Author(s): Nakai K, Yoneda K, Haba R, Kushida Y, Katsuki N, Moriue J, Moriue T, Ishikawa E, Inoue S, Kubota Y
  • Journal Title: J Dermatol Volume: 41 Pages: 171-172
  • Peer Reviewed
• [Journal Article] Deranged epidermal differentiation in kl/kl mouse and the effects of βKlotho siRNA on the differentiation of HaCaT cells. (2013)
  • Author(s): Nakai K, Yoneda K, Haba R, Kushida Y, Katsuki N, Moriue T, Kosaka H, Kubota Y, Inoue S
  • Journal Title: Exp Dermatol Volume: 22 Pages: 772-774
  • Peer Reviewed
• [Journal Article] Reduced expression of epidermal growth factor receptor, E-cadherin, and occludin in the skin of flaky tail mice is due to filaggrin and loricrin deficiencies. (2012)
  • Author(s): Nakai K, Yoneda K, Hosokawa Y, Moriue T, Presland RB, Fallon PG, Kabashima K, Kosaka H, Kubota Y.
  • Journal Title: American Journal of Pathology Volume: 181(3) Pages: 969-977
  • Peer Reviewed
• [Presentation] Free radical production in LPS-treated skin of atopic dermatitis mouse model (2014)
  • Author(s): Kozo Nakai, Maria B Kadiiska, Jin-Jie Jiang, Ronald P. Mason, Tetsuya Moriue, Kozo Yoneda, and Yasuo Kubota
  • Organizer: 日本研究皮膚科学会 第39回年次学術大会・総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] Reduced expression of EGF receptor, E-cadherin and occludin is due to loricrin deficiency in the skin of flaky tail mice (2011)
  • Author(s): 中井浩三
  • Organizer: 日本研究皮膚科学会第３６会年次学術大会・総会
  • Place of Presentation: 京都
• [Presentation] betaKlotho is required for the epidermal differentiation, and its expression is suppressed in human nonmelanoma skin cancer
  • Author(s): Kozo Nakai, Shigeaki Inoue, Reiji Haba, Yoshio Kushida, Nahomi Katsuki, Yoichiro Hosokawa, Tetsuya Moriue, Kozo Yoneda and Yasuo Kubota
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinbourgh
• [Presentation] 1. フリーラジカル・酸化ストレス制御によるアレルギー性皮膚疾患治療をめざして
  • Author(s): 中井浩三
  • Organizer: 日本皮膚科学会西部支部学術大会
  • Place of Presentation: 鹿児島
  • Invited
• [Presentation] Free radical production in LPS-treated skin of atopic dermatitis mouse model
  • Author(s): Kozo Nakai, Maria B Kadiiska, Jin-Jie Jiang, Ronald P. Mason, Tetsuya Moriue, Kozo Yoneda, and Yasuo Kubota
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura
• [Presentation] Reduced expression of EGF receptor, E-cadherin and occludin is due to loricrin deficiency in the skin of flaky tail mice
  • Author(s): Kozo Nakai, Kozo Yoneda, Yoichiro Hosokawa, Tetsuya Moriue, Yasuo Kubota
  • Organizer: 第36回日本研究皮膚科学会
  • Place of Presentation: 京都
• [Book] Filaggrin Jacob P. Thyssen Howard I. Maibach Editors (2014)
  • Author(s): Nakai K, Yoneda K, Kubota Y
  • Total Pages: 373
  • Publisher: Springer