Regulation of epidermal innate immunity by Smurf/Arkadia

• Project/Area Number: 25293245
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Ehime University
• Principal Investigator: Koji Sayama 愛媛大学, 医学(系)研究科(研究院), 教授 (80187286)
• Co-Investigator(Kenkyū-buntansha): Toyama Mikiko 愛媛大学, 大学院医学系研究科, 准教授 (60263935) ; Shiraishi Ken 愛媛大学, 医学部附属病院, 講師 (80710863) ; 白方 裕司 愛媛大学, 医学(系)研究科(研究院), 准教授 (50226320)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
• Keywords: Innate immunity / keratinocyte / epidermis / TGF-beta / Smad / 自然免疫 / 角化細胞 / smad / KOマウス / 表皮角化細胞 / インフラマソーム / アレルギー

Outline of Final Research Achievements

Function of Smurf and Arkadia was analyzed in keratinocytes. Stimulation with TGF-beta enhanced Smad2/3 phosphorylation and Smad7 expression. While TGF-beta stimulation enhaced Smurf1/2 expression, it did not enhance the expression of Arkadia. The phosphorylation of Smad2/3 and the expression of Smad7 were significantly enhanced by reducing Smurf by using shRNA. On the other hand, suppression of Arkadia by shRNA reduced the phosphorylation of Smad2/3 and the expression of Smad7. Furthermore, suppressive effect of TGF-beta on cell growth and migration was enhanced by knockdown of Smurf.

Research Products

• [Journal Article] Cell motion predicts human epidermal stemness. (2015)
  • Author(s): Nanba D, Toki F, Tate S, Imai M, Matsushita N, Shiraishi K, Sayama K, Toki H, Higashiyama S, Barrandon Y.
  • Journal Title: J Cell Biol. Volume: 209 Issue: 2 Pages: 305-315
  • DOI: 10.1083/jcb.201409024
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cefcapene pivoxil hydrochloride is a potentially new treatment for palmoplantar pustulosis with pustulotic arthro-osteitis (2015)
  • Author(s): Murakami M, Masuda K, Utsunomiya R, Oda F, Namba C, and Sayama K.
  • Journal Title: Dermatology Volume: 231 Issue: 4 Pages: 304-311
  • DOI: 10.1159/000439401
  • Peer Reviewed
• [Journal Article] Vesicular LL-37 contributes to inflammation of the lesional skin of palmoplantar pustulosis. (2014)
  • Author(s): Murakami M, Kaneko T, Nakatsuji T, Kameda K, Okazaki H, Dai X, Hanakawa Y, Tohyama M, Ishida-Yamamoto A, Sayama K.
  • Journal Title: PLoS One. Volume: 9 Issue: 10 Pages: 304-311
  • DOI: 10.1371/journal.pone.0110677
  • Peer Reviewed / Open Access
• [Journal Article] Eccrine sweat contains IL-1α, IL-1β and IL-31 and activates epidermal keratinocytes as a danger signal. (2013)
  • Author(s): Dai X, Okazaki H, Hanakawa Y, Murakami M, Tohyama M, Shirakata Y, Sayama K.
  • Journal Title: PLoS One. Volume: ８ Issue: 7 Pages: 1-8
  • DOI: 10.1371/journal.pone.0067666
  • Peer Reviewed
• [Journal Article] Pressure sore-like ulcers on acneiform papules caused by EGFR inhibitors (2013)
  • Author(s): Miyawaki S, Tohyama M, Irifune K, Ito R, and Sayama K.
  • Journal Title: Int Wound J Volume: 21 Issue: 5 Pages: 1-2
  • DOI: 10.1111/iwj.12070
  • Peer Reviewed
• [Journal Article] The “rat bite” streptbacillosis caused the acute generalized pustular bacterid but not the palmoplantar pustulosis (2013)
  • Author(s): Murakami M, Ishida-Yamamoto A, Morhenn VB, and Sayama K.
  • Journal Title: The Lancet Infect Dis Volume: 13 Issue: 8 Pages: 655-656
  • DOI: 10.1016/s1473-3099(13)70103-8
  • Peer Reviewed
• [Presentation] Smurfs E3 ubiquitin ligases negatively regulate TGF-beta signaling in keratinocytes (2015)
  • Author(s): Ken Shiraishi, Xiuju Dai, Masamoto Murkami, Mikiko Tohyama, Natsuki Matsushita, TAkeshi Imamura, Koji Sayama
  • Organizer: Society for Investigative Dermatology, 2015 Annual Meeting
  • Place of Presentation: Atlanta, GA, U.S.A.
  • Year and Date: 2015-05-06 – 2015-05-09
• [Presentation] Smurfs E3 ubiquitin ligases negatively regulate TGF-beta signaling in keratinobytes (2015)
  • Author(s): Shiraishi K, Dai X, Murakami M, Tohyama M, Matsushita N, Imamura T, and Sayama K.
  • Organizer: Society for Investigative Dermatolgy 2015 Annual meeting
  • Place of Presentation: Atlanta GA, USA
  • Year and Date: 2015-05-06
  • Int'l Joint Research
• [Presentation] CISH suppresses IL-17-induced CCL20 production from epidermal keratinocytes via inhibition of the Src/MEK/ERK pathway (2013)
  • Author(s): Tohyama M, Shirakata Y, Hanakawa Y, Dai X, Okazaki H, Murakami M, Hashimoto K, and Sayama K.
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinburgh, UK
• [Presentation] Human cathelicidin (hCAP18/LL37) in pustules contributes to the pathogenesis of palmoplantar pustulosis (2013)
  • Author(s): Murakami M, Okazaki H, Shirakata Y, Kaneko T, Ishida-Yamamoto A, Iizuka H, Morhenn VB, Gallo RL, and Sayama K
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinburgh, UK
• [Presentation] Eccrine sweat simulates the release of IL-8 via IL-1 from epidermal keratinocytes as danger signal (2013)
  • Author(s): Okazaki H, Dai X, Murakami M, Hanakawa Y, Tohyama M, Shirakata Y, and Sayama K
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinburgh, UK