Development of novel therapy for skin inflammatory diseases targeting PKCeta

• Project/Area Number: 22590105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Showa University
• Principal Investigator: OHBA Motoi 昭和大学, 腫瘍分子生物学研究所, 講師 (70297018)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ゲノム創薬 / 分子標的薬 / PKC / 炎症

Research Abstract

My goal is to develop a novel therapeutic method for severe skin inflammatory diseases including atopic dermatitis(AD) targeting PKCη. Inhibition of PKCη activity by using the dominant negative type of PKCη improved the symptom such as erosiom and fissure on the back skin of AD model mice. Moreover, novel siRNA sequences for PKCη, which significantly repress the PKCη gene expression, were found.Furthermore, Stimulus by wound and reactive oxygen species existed as an upstream signal of PKCη, suggesting that these signals enhance AD symptom via the increase of PKCη activity.

Research Products

• [Journal Article] Activation of PAR-2 stimulates sVEGFR-1 release via EGF receptortransactivation in endothelial cells (2010)
  • Author(s): Bahjat Al-Ani, Peter W. Hewett, Melissa J. Cudmore, Takeshi Fujisawa, Mahmoud, Saifeddine, Hannah Williams, Wenda Ramma, Samir Sissaoui, Padma-Sheela, Jayaraman, Motoi Ohba, Shakil Ahmad, Morley D.Hollenberg and Asif Ahmed.
  • Journal Title: Hypertention Volume: 55(3) Issue: 3 Pages: 689-97
  • DOI: 10.1161/hypertensionaha.109.136333
  • Peer Reviewed
• [Journal Article] Protein kinase C δ and η differently regulate the expression of loricrin and Jun family proteins in human keratinocytes Biochem (2010)
  • Author(s): Kamioka N, Akahane T, Kohno Y, Kuroki T, Iijima M, Honma Iand Ohba M
  • Journal Title: Biophys. Res. Commun Volume: 394 Issue: 1 Pages: 106-111
  • DOI: 10.1016/j.bbrc.2010.02.125
  • Peer Reviewed
• [Journal Article] B lymphocyte-induced maturation protein 1 is a novel target gene of aryl hydrocarbon receptor. (2010)
  • Author(s): Ikuta T, Ohba M., Zouboulis C., Fujii-Kuriyama Y., Kawajiri K
  • Journal Title: J. Derm. Sci Volume: 58(3) Issue: 3 Pages: 211-6
  • DOI: 10.1016/j.jdermsci.2010.04.003
  • Peer Reviewed
• [Journal Article] ヒト三次元培養皮膚への遺伝子導入法の確立と表皮分化へのCキナーゼの関与 (2010)
  • Author(s): 上岡 なぎさ、本間 生夫、赤羽 智子、河野葉子、飯島 正文、大場 基
  • Journal Title: 昭和医学会雑誌2010 Volume: Vol. 70 (3) Pages: 253-262
  • NAID: 130000852909
  • Peer Reviewed
• [Journal Article] Protein kinase C delta and eta differently regulate the expression of loricrin and Jun family proteins in human keratinocytes (2010)
  • Author(s): Kamioka N., Ohba M.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 394 Pages: 106-111
  • Peer Reviewed
• [Journal Article] Activation of PAR-2 stimulates sVEGFR-1 release via EGF receptortransactivation in endothelial cells (2010)
  • Author(s): Bahjat Al-Ani, Ohba M.
  • Journal Title: Hypertention Volume: 55 Pages: 689-697
  • Peer Reviewed
• [Journal Article] B lymphocyte-induced maturation protein 1 is a novel target gene of aryl hydrocarbon receptor. (2010)
  • Author(s): Ikuta T., Ohba M.
  • Journal Title: J.Derm.Sci. Volume: 58 Pages: 211-216
  • Peer Reviewed
• [Presentation] Differential role of protein kinase C ηin cell growth between squamous cell carcinoma and adenocarcinoma (2013)
  • Author(s): Motoi Ohba, Tohru Ohmori, Toshio Kurokiand Etsuko Toya
  • Organizer: 19thInternational Charles Heidelberger Symposium In Cancer research
  • Place of Presentation: Kagoshima, Japan
• [Presentation] Differential role of protein kinase C eta in cell growth between squamous cell carcinoma and adenocarcinoma. (2013)
  • Author(s): 大場 基
  • Organizer: 19th International Charles Heidelberger Symposium On Cancer Research
  • Place of Presentation: 鹿児島県鹿児島市
• [Presentation] 毛包上皮幹細胞の永代培養法と分化誘導法の確立 (2011)
  • Author(s): 大場 基
  • Organizer: 昭和大学共同研究 研究成果発表会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-21
• [Remarks]
  • URL: http://www10.showa-u.ac.jp/~molonco/index/
• [Patent(Industrial Property Rights)] PKCη発現抑制系 (2012)
  • Inventor(s): 大場 基
  • Industrial Property Rights Holder: 大場 基
  • Industrial Property Number: 2012-246772
  • Filing Date: 2012-11-08
• [Patent(Industrial Property Rights)] 特許権 (2012)
  • Inventor(s): 大場 基
  • Industrial Property Rights Holder: 大場 基
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-11-08