Role of PLC epsilon-PKC myu pathway in skin inflammation, skin cancer, cataract, and psoriasis vulgaris.

• Project/Area Number: 26461692
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tohoku Medical and Pharmaceutical University (2016); Kobe University (2014-2015)
• Principal Investigator: OKA Masahiro 東北医科薬科大学, 医学部, 教授 (30252761)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 尋常性乾癬 / ホスホリパーゼＣε / プロテインキナーゼCμ / マウス / 皮膚 / 紫外線発がん / 創傷治癒 / 角化細胞 / トランスジェニックマウス / 紫外線 / phospholipase C epsilon / STAT3 / 乾癬 / 好中球 / 皮膚がん / ホスホリパーゼC イプシロン / 皮膚発癌 / アポトーシス

Outline of Final Research Achievements

Phospholipase C (PLC) epsilon is a phosphoinositide-specific PLC regulated by small GTPases including Ras and Rap. In order to investigate the role of PLC epsilon in the skin, we created transgenic mice over expressing PLC epsilon in epidermal leratinocytes. The resulting transgenic mice spontaneously developed skin inflammation like psoriasis vulgaris as characterized by formation of adherent silvery scales, acanthosis, parakeratosis, and infiltration of neutrophils in the epidermis, and aberrant infiltration of immune cells such as T cells and dendritic cells. After observing that protein kinase C μ (PKCμ) is activated after activation of PLC epsilon, we created transgenic mice overexpressing PKCμ in epidermal leratinocytes (K5-PKCμ-TG). However, the K5-PKCμ-TG did not show skin changes seen in psoriasis vulgaris. These results indicate that overexpression of PLC epsilon induces psoriasis-like skin changes but these changes are not mediated by PKCμ.

Research Products

• [Journal Article] Mixed connective tissue disease with bilateral erythematous palpebral edema and targetoid skin lesions. (2017)
  • Author(s): Sakaguchi, M., Takeda, T., Kodera, T., Murakami, K., Oka, M.
  • Journal Title: Eur. J. Dermatol. Volume: 27 Issue: 1 Pages: 64-65
  • DOI: 10.1684/ejd.2016.2902
  • Peer Reviewed / Open Access
• [Journal Article] Cutaneous Rosai-Dorfman disease associated with uveitis (2017)
  • Author(s): Fukumoto T, Oka M, Masaki T, Sakaguchi M, Fukunaga A, Norose K, Sarayama Y, Imai H, Nishigori C
  • Journal Title: Eur J Dermatol Volume: 27 Issue: 1 Pages: 85-86
  • DOI: 10.1684/ejd.2016.2885
  • Peer Reviewed / Open Access
• [Journal Article] Malignant melanoma with bone marrow involvement diagnosed from hypercalcemia: Development of a neural cell adhesion molecule stain. (2017)
  • Author(s): Fukumoto, T., Sakaguchi, M., Oka, M., Nishimura, M., Mukohara, T., Nishigori, C.
  • Journal Title: J. Dermatol. Volume: 44 Issue: 5
  • DOI: 10.1111/1346-8138.13718
  • Peer Reviewed / Open Access
• [Journal Article] High expression of Mcl-1L via the MEK-ERK-phospho-STAT3 (Ser727) pathway protects melanocytes and melanoma from UVB-induced apoptosis. (2016)
  • Author(s): Fukumoto-T, Iwasaki-T, Okada-T, Hashimoto-T, Moon-Y, Sakaguchi-M, Fukami-Y, Nishigori-C, Oka-M.
  • Journal Title: Genes Cells. Volume: 21 Issue: 2 Pages: 185-199
  • DOI: 10.1111/gtc.12330
  • Peer Reviewed / Open Access
• [Journal Article] Acute generalized exanthematous pustulosis induced by Mycoplasma pneumoniae infection. (2016)
  • Author(s): Taguchi K, Oka M, Bito T, Nishigori C.
  • Journal Title: J Dermatol Volume: 43 Issue: 1 Pages: 113-114
  • DOI: 10.1111/1346-8138.13151
  • Peer Reviewed / Open Access
• [Journal Article] Mucosal lichen sclerosus/lichen planus overlap syndrome with cutaneous lesions of lichen sclerosus. (2016)
  • Author(s): Yahiro C, Oka M, Fukunaga A, Fukumoto T, Sakaguchi M, Takahashi Y, Komori T, Ueda T, Nishigori C.
  • Journal Title: Eur J Dermatol Volume: in press Issue: 2 Pages: 204-205
  • DOI: 10.1684/ejd.2015.2715
  • Peer Reviewed / Open Access
• [Journal Article] Single, blue nevus-like localized argyria. (2016)
  • Author(s): Nagano T, Oka M, Horikawa T, Nishigori C, Kotera M.
  • Journal Title: J Dermatol Volume: in press Issue: 11 Pages: 1359-1360
  • DOI: 10.1111/1346-8138.13387
  • Peer Reviewed / Open Access
• [Journal Article] Telangiectatic lichen sclerosus on the cheek successfully treated with topical tacrolimus. (2016)
  • Author(s): Jimbo H, Oka M, Fukumoto T, Yoshioka A, Miki Y, Sakaguchi M, Ogura K, Nishigori C.
  • Journal Title: Eur J Dermatol Volume: in press Issue: 3 Pages: 321-322
  • DOI: 10.1684/ejd.2016.2769
  • Peer Reviewed / Open Access
• [Journal Article] Telangiectatic lichen sclerosus on the cheek successfully treated with topical tacrolimus. (2016)
  • Author(s): Jimbo H, Oka M, Fukumoto T, Yoshioka A, Miki Y, Sakaguchi M, Ogura K, Nishigori C.
  • Journal Title: Eur J Dermatol Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Mucosal lichen sclerosus/lichen planus overlap syndrome with cutaneous lesions of lichen sclerosus. (2016)
  • Author(s): Yahiro C, Oka M, Fukunaga A, Fukumoto T, Sakaguchi M, Takahashi Y, Komori T, Ueda T, Nishigori C.
  • Journal Title: Eur J Dermatol Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Acquired dermal melanocytosis confined to the palm with a review of published cases of acquired dermal melanocytosis on the hands. (2015)
  • Author(s): Nakauchi E, Oka M, Fukumoto T, Sakaguchi M, Nishigori C.
  • Journal Title: J Dermal Volume: 42 Issue: 6 Pages: 1-5
  • DOI: 10.1111/1346-8138.13232
  • Peer Reviewed / Open Access
• [Journal Article] Multiple apocrine poromas: a new case report. (2015)
  • Author(s): Nishioka M, Kunisada M, Fujiwara N, Oka M, Funasaka Y, Nishigori C.
  • Journal Title: J Cutan Pathol Volume: 42 Issue: 11 Pages: 894-896
  • DOI: 10.1111/cup.12574
  • Peer Reviewed / Open Access
• [Journal Article] Influence of neutralizing antibodies to adalimumab and infliximab on the treatment of psoriasis. (2014)
  • Author(s): Bito, T., Nishikawa, R., Hatakeyama, M., Kikusawa, A., Kanki, H., Nagai, H., Sarayama, Y., Ikeda, T., Yoshizaki, H., Seto, H., Adachi, A., Horikawa, T., Oka, M., Nishigori, C.
  • Journal Title: Br. J. Dermatol. Volume: 170 Issue: 4 Pages: 922-929
  • DOI: 10.1111/bjd.12791
  • Peer Reviewed / Open Access
• [Journal Article] Unilateral eruptive seborrheic keratoses associated with hepatic hemangiomas. (2014)
  • Author(s): Ikkaku, N., Oka, M., Yamada, Y., Uda, K., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 24 Issue: 1 Pages: 109-110
  • DOI: 10.1684/ejd.2013.2229
  • Peer Reviewed / Open Access
• [Journal Article] Diffuse plane normolipemic xanthoma associated with chronic myelomonocytic leukemia-1. (2014)
  • Author(s): Oka, M., Okamura, A., Kawano, S., Fukumoto, T., Sakaguchi, M., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 24 Issue: 1 Pages: 112-113
  • DOI: 10.1684/ejd.2013.2256
  • Peer Reviewed
• [Presentation] 外陰部病変および外陰外病変を有し、かつ、口腔粘膜に扁平苔癬を合併した硬化性萎縮性苔癬の1例 (2014)
  • Author(s): 南 知里、福本 毅、坂口正展、竹内聖二、福永 淳、岡 昌宏、高橋佑輔、古森孝英、植田透子、錦織千佳子
  • Organizer: 日本皮膚科学会中部支部学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-25 – 2014-10-26
• [Presentation] Ultraviolet B-induced up-regulation of Mcl-1 mediated by MEK–ERK1/2–STAT3 signaling pathway has a protective role in apoptosis in melanocytes (2014)
  • Author(s): Takeshi Fukumoto, Masahiro Oka, Masanobu Sakaguchi, Chikako Nishigori , Tetsushi Iwasaki, Takanori Hashimoto, Youbin Moon, Yasuo Fukami, Taro Okada
  • Organizer: 2014 International Pigment Cell Conference
  • Place of Presentation: Singapore
  • Year and Date: 2014-09-04 – 2014-09-07