Defective maintenance of pH of stratum corneum can induce atopic dermatitis

• Project/Area Number: 25860958
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Oita University
• Principal Investigator: Sakai Takashi 大分大学, 医学部, 助教 (20624290)
• Research Collaborator: HATANO YUTAKA ; FUJIWARA SAKUHEI ; HIROSE HARUNA ; ZHANG WEI ; Jeong Se Kyoo ; Elias Peter M.
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: アトピー性皮膚炎 / 角層pH / フィラグリン / Flaky-tailマウス

Outline of Final Research Achievements

We investigated the homeostasis of stratum coreneum (SC) pH on the pathogenesis of atopic dermatitis (AD). In consequence, it was confirmed that defective maintenance of pH of SC is correlated with preferential emergence and exacerbation of AD-like dermatitis in flaky tail mice. Furthermore, we showed combined benefits of a PAR2 inhibitor and SC acidification for murine AD, suggesting the importance of homeostasis of SC pH and maintenance of acidic SC pH on the pathogenesis of AD.

Research Products

• [Int'l Joint Research] NeoPharm Co., Ltd.(韓国)
• [Int'l Joint Research] Veterans Affairs Medical Center./University of California.(米国)
• [Journal Article] Wy14643, an agonist for PPARα, down-regulates expression of TARC and RANTES in cultured human keratinocytes (2017)
  • Author(s): Zhang W, Sakai T, Fujiwara S, Hatano Y
  • Journal Title: Experimental Dermatology Volume: 印刷中 Issue: 5 Pages: 457-459
  • DOI: 10.1111/exd.13245
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Betamethasone Butyrate Propionate Inhibits the Induction of Thymic Stromal Lymphopoietin in Cultured Normal Human Keratinocytes. (2016)
  • Author(s): Zhang W, Sakai T, Hatano Y, Fujiwara S.
  • Journal Title: Ann Dermatol. Volume: 28(6) Issue: 6 Pages: 772-775
  • DOI: 10.5021/ad.2016.28.6.772
  • Peer Reviewed
• [Journal Article] Combined Benefits of a PAR2 Inhibitor and Stratum Corneum Acidification for Murine Atopic Dermatitis. (2016)
  • Author(s): Sakai T, Hatano Y, Matsuda-Hirose H, et al.
  • Journal Title: J Invest Dermatol Volume: 136 Issue: 2 Pages: 538-41
  • DOI: 10.1016/j.jid.2015.11.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Knockdown of either filaggrin or loricrin increases the productions of interleukin (IL)-1α, IL-8, IL-18 and granulocyte macrophage colony-stimulating factor in stratified human keratinocytes (2015)
  • Author(s): Takashi Sakai, Yutaka Hatano, Wei Zhang, Sakuhei Fujiwara, Ryo Nishiyori.
  • Journal Title: Journal of Dermatological Science Volume: 80 Issue: 2 Pages: 158-160
  • DOI: 10.1016/j.jdermsci.2015.09.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Atopic dermatitis-like dermatitis emerges unevenly on different sites in flaky tail mice. (2015)
  • Author(s): Takashi Sakai, Yutaka Hatano, Haruna Matsuda-Hirose, Ryo Nishiyori, Sakuhei Fujiwara.
  • Journal Title: Journal of Dermatological Science Volume: 78 Issue: 2 Pages: 151-153
  • DOI: 10.1016/j.jdermsci.2015.01.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Defective maintenance of pH of stratum corneum is correlated with preferential emergence and exacerbation of atopic-dermatitis-like dermatitis in flaky-tail mice. (2014)
  • Author(s): Takashi Sakai, Yutaka Hatano, Wei Zhang, Sakuhei Fujiwara.
  • Journal Title: Journal of Dermatological Science Volume: 印刷中 Issue: 3 Pages: 222-228
  • DOI: 10.1016/j.jdermsci.2014.01.012
  • Peer Reviewed
• [Presentation] Knockdown of either filaggrin or loricrin increases the productions of IL-1α, IL-8, IL-18 and GM-CSF in stratified human keratinocytes (2015)
  • Author(s): Takashi Sakai, Ryo Nishiyori, Yutaka Hatano, Wei Zhang, Sakuhei Fujiwara.
  • Organizer: 40th Annual Meeting of JSID
  • Place of Presentation: Okayama, Japan
  • Year and Date: 2015-12-11
  • Int'l Joint Research
• [Presentation] Combined benefits of a protease-activated receptor 2 inhibitor and stratum corneum acidification for murine atopic dermatitis (2015)
  • Author(s): Takashi Sakai, Yutaka Hatano, Haruna Matsuda-Hirose, Wei Zhang, Daisuke Takahashi, Se Kyoo Jeong, Peter M. Elias, Sakuhei Fujiwara.
  • Organizer: 45th Annual ESDR Meeting
  • Place of Presentation: Rotterdam, The Netherlands
  • Year and Date: 2015-09-09
  • Int'l Joint Research
• [Presentation] Spontaneous atopic-dermatitis-like dermatitis emerges on face and neck but not whole body in flaky-tail mice. (2014)
  • Author(s): Takashi Sakai, Yutaka Hatano, Haruna Hirose, Wei Zhang, Sakuhei Fujiwara.
  • Organizer: 3rd Eastern Asia Dermatology Congress
  • Place of Presentation: Jeju, Korea.
  • Year and Date: 2014-09-24 – 2014-09-26
• [Presentation] Increased sensitivity to stratum corneum neutralization favors the development of dermatitis in flaky-tail mice. (2013)
  • Author(s): Takashi Sakai, Yutaka Hatano, Sakuhei Fujiwara.
  • Organizer: International Investigative Dermatology 2013
  • Place of Presentation: Edinburgh, Scotland.