Role of phospholipase C epsilon in ultraviolet-induced skin carcinogenesis, skin inflammation, cataract, and psoriasis

• Project/Area Number: 23591645
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kobe University
• Principal Investigator: OKA Masahiro 神戸大学, 医学(系)研究科(研究院), 准教授 (30252761)
• Co-Investigator(Kenkyū-buntansha): EDAMATSU Hironori 神戸大学, 大学院医学研究科, 助教 (70335438)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ホスホリパーゼＣ / 紫外線 / 皮膚 / 乾癬 / 発癌 / 白内障 / マウス / 角膜 / ホスホリパーゼC イプシロン / 創傷治癒 / 好中球 / ホスホリパーゼCε / 皮膚発癌 / 皮膚炎症 / ホスホリパーゼCイプシロン / 炎症

Research Abstract

Phospholipase C (PLC) epsilon is a phosphoinositide-specific PLC regulated by small GTPases including Ras and Rap. In order to investigate the role of PLCe in the skin, we created transgenic mice overexpressing PLCe in epidermal leratinocytes (K5-PLCe-TG). The resulting transgenic mice spontaneously developed skin inflammation 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. When mice were irradiated with ultraviolet B, most wild mice developed erosions and ulcers in the skin, whereas the K5-PLCe-TG mice were resistant to UVB-induced skin damages. In addition, it was revealed that the ability of wound healing in the K5-PLCe-TG mice is increased compared to that in wild mice.

Research Products

• [Journal Article] Epstein-Barr virus associated methotrexate-induced accelerated rheumatoid nodulosis. (2014)
  • Author(s): Shimoura, N., Fukunaga, A., Nagai, H., Oka, M., Nishigori, C.
  • Journal Title: Acta Derm. Venereol. Volume: - Pages: 100-101
  • DOI: 10.2340/00015555-1866
  • NAID: 120005723183
  • Peer Reviewed
• [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
• [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] 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] Multiple apocrine poromas: A new case report. (2014)
  • Author(s): Nishioka, M., Kunisada, M., Fujiwara, N., Oka, M., Funasaka, Y., Nishigori, C.
  • Journal Title: J. Cutan. Pathol. Volume: -
  • Peer Reviewed
• [Journal Article] Cutaneous plasmacytosis in an 88-year-old woman successfully treated with low-dose oral corticosteroid. (2013)
  • Author(s): Oka, M., Kunisada, M., Nishigori, C.
  • Journal Title: Int. J. Dermatol. Volume: 52 Issue: 11 Pages: 1412-1414
  • DOI: 10.1111/j.1365-4632.2011.05221.x
  • Peer Reviewed
• [Journal Article] Onychomycosis as a warning sign for peripheral arterial disease. (2013)
  • Author(s): Fukunaga, A., Washio, K., Ogura, K., Taguchi, K., Chiyomaru, K., Ohno, Y., Masaki, T., Nagai, H., Nagano, T., Oka, M., Nishigori, C.
  • Journal Title: Acta Derm. Venereol. Volume: 93 Issue: 6 Pages: 747-748
  • DOI: 10.2340/00015555-1576
  • NAID: 120005723197
  • Peer Reviewed
• [Journal Article] Severe xanthomatosis with prominent tuberous xanthomas on the cheeks and the nasal dorsum in a patient with type IIa hyperlipoproteinemia. (2013)
  • Author(s): Fujiwara, S., Oka, M., Kunisada, M., Honjo, K., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 23 Issue: 4 Pages: 517-518
  • DOI: 10.1684/ejd.2013.2063
  • Peer Reviewed
• [Journal Article] Complete clinical remission of tumor-stage granulomatous mycosis fungoides after treatment with PUVA, skin electron irradiation, oral retinoid, and systemic interferon-γ. (2013)
  • Author(s): Yamada, Y., Oka, M., Fujiwara, S., Nishioka, E., Okamoto, Y., Hayashibe, K., Nishigori, C.
  • Journal Title: Int. J. Dermatol. Volume: 52 Issue: 7 Pages: 893-895
  • DOI: 10.1111/j.1365-4632.2011.05032.x
  • Peer Reviewed
• [Journal Article] IgG4-related skin manifestations in patients with IgG4-related disease (2013)
  • Author(s): Ikeda, T., Oka, M., Shimizu, H., Hatakeyama, M., Kanki, H., Kunisada, M., Tsuji, G., Morinobu, A., Kumagai, S., Azumi, A., Negi, A., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 23(2) Issue: 2 Pages: 241-245
  • DOI: 10.1684/ejd.2013.1958
  • Peer Reviewed
• [Journal Article] A case of multiple facial clear cell acanthoma.successfully treated with cryotherapy. (2013)
  • Author(s): Hatakeyama, A., Oka, M., Fukunaga, A., Kunisada, M., Funasaka, Y., Nishigori, C.
  • Journal Title: Indian J. Dermatol. Volume: 58 Issue: 2 Pages: 162-162
  • DOI: 10.4103/0019-5154.108122
  • Peer Reviewed
• [Journal Article] Generalized annular elastolytic giant cell granuloma with sparing of striae distensae. (2013)
  • Author(s): Oka, M., Kunisada, M., Nishigori, C.
  • Journal Title: J. Dermatol. Volume: 40 Issue: 3 Pages: 220-222
  • DOI: 10.1111/1346-8138.12048
  • Peer Reviewed
• [Journal Article] Unilateral lower leg purpura (2013)
  • Author(s): Ogawa, S., Oka, M., Kunisada, M., Nishigori, C.
  • Journal Title: Dermatol. Online J. Volume: 19(1) Pages: 16-16
  • Peer Reviewed
• [Journal Article] IgG4-related skin manifestations in patients with IgG4-related disease. (2013)
  • Author(s): Ikeda, T., Oka, M., Shimizu, H., Hatakeyama, M., Kanki, H., Kunisada, M., Tsuji, G., Morinobu, A., Kumagai, S., Azumi, A., Negi, A., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 23 Pages: 241-245
  • Peer Reviewed
• [Journal Article] Unilateral lower leg purpura. (2013)
  • Author(s): Ogawa, S., Oka, M., Kunisada, M., Nishigori, C.
  • Journal Title: Dermatol. Online J. Volume: 19 Pages: 16-16
  • Peer Reviewed
• [Journal Article] Role and Regulation of STAT3Phosphorylation at Ser727in Melanocytes and Melanoma Cells (2012)
  • Author(s): Sakaguchi, M., Oka, M., Iwasaki, T., Fukami, Y., Nishigori, C.
  • Journal Title: J Invest Dermatol Volume: (掲載確定) Issue: 7 Pages: 1877-1885
  • DOI: 10.1038/jid.2012.45
  • Peer Reviewed
• [Journal Article] Localized cutaneous fusariosis after long-term topical application of corticosteroids in a healthy elderly woman. (2012)
  • Author(s): Yamada, Y., Nishioka, G., Makimura, K., Oka, M
  • Journal Title: Eur. J. Dermatol. Volume: 22 Issue: 4 Pages: 555-559
  • DOI: 10.1684/ejd.2012.1753
  • Peer Reviewed
• [Journal Article] Prolonged varicella-zoster virus reinfection in an adult after unrelated cord blood transplantation. (2012)
  • Author(s): Oka, M., Kunisada, M., Oba, Y., Okamura, A., Nishigori., C.
  • Journal Title: Indian J. Dermatol. Volume: 57 Issue: 5 Pages: 399-400
  • DOI: 10.4103/0019-5154.100500
  • Peer Reviewed
• [Journal Article] Unilateral aquagenic wrinkling of the palms with a peculiar clinical course. (2012)
  • Author(s): Ibusuki, C., Oka, M., Fukunaga, A., Kunisada, M., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 22 Issue: 5 Pages: 679-680
  • DOI: 10.1684/ejd.2012.1792
  • Peer Reviewed
• [Journal Article] Case of recurrent Sweet’s syndrome in a patient with relapsing polychondritis and myelodysplastic syndrome. (2012)
  • Author(s): Washio, K., Oka, M., Ohno, K., Shimizu, H., Kawano, S., Kunisada, M., Nishigori, C.
  • Journal Title: J. Dermatol. Volume: 39 Issue: 8 Pages: 731-733
  • DOI: 10.1111/j.1346-8138.2011.01403.x
  • Peer Reviewed
• [Journal Article] Ciliated cyst of the vulva in an elderly woman. (2012)
  • Author(s): Kyo, S., Oka, M., Bito T., Hatakeyama M., Kunisada M., Nishigori C.
  • Journal Title: Eur. J. Dermatol. Volume: 22 Issue: 4 Pages: 559-560
  • DOI: 10.1684/ejd.2012.1759
  • Peer Reviewed
• [Journal Article] Peristomal skin ulcer with intestinal metaplasia. (2012)
  • Author(s): Ono, R., Oka, M., Sakaguchi, M.,Nishioka, E., Kawakami, F., Nagano, T., Kunisada, M., Nishigori, C.
  • Journal Title: Br. J. Dermatol. Volume: 167 Issue: 1 Pages: 204-206
  • DOI: 10.1111/j.1365-2133.2012.10819.x
  • Peer Reviewed
• [Journal Article] Intradermal nodular fasciitis. (2012)
  • Author(s): Terai, M., Oka, M., Kunisada, M., Kawakami, F., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 22 Issue: 2 Pages: 285-286
  • DOI: 10.1684/ejd.2012.1657
  • Peer Reviewed
• [Journal Article] Recalcitrant pruritic urticarial papules and plaques of pregnancy with a prolonged course after delivery. (2012)
  • Author(s): Terai, M., Oka, M., Tsujimoto, M., Kunisada, M., Tada, S., Bito, T., Nishigori. C.
  • Journal Title: Eur. J. Dermatol. Volume: 22 Issue: 1 Pages: 136-137
  • DOI: 10.1684/ejd.2011.1574
  • Peer Reviewed
• [Journal Article] Subcutaneous lobular capillary hemangioma with sonography and computed tomography findings. (2012)
  • Author(s): Kikusawa, A., Oka, M., Shimizu, H., Tsujimoto, M., Marui, Y., Yokogawa, S., Kita, Y., Kunisada, M., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 22 Issue: 2 Pages: 276-277
  • DOI: 10.1684/ejd.2012.1652
  • Peer Reviewed
• [Journal Article] Subcutaneous lobular capillary hemangioma with sonography and computed tomography findings (2012)
  • Author(s): Ayuko Kikusawa, Masahiro Oka, Hideki Shimizu,1 Mariko Tsujimoto, Yumiko Marui, Shusaku Yokogawa, Yasufumi Kita, Makoto Kunisada, and Chikako Nishigori
  • Journal Title: European Journal of Dermatology Volume: 22 Pages: 276-277
  • Peer Reviewed
• [Journal Article] Intradermal nodular fasciitis (2012)
  • Author(s): Terai, M., Oka, M., Kunisada, M., Kawakami, F., Nishigori, C.
  • Journal Title: European Journal of Dermatology Volume: 22 Pages: 285-286
  • Peer Reviewed
• [Journal Article] Recalcitrant pruritic urticarial papules and plaques of pregnancy with a prolonged course after delivery (2012)
  • Author(s): Terai, M., Oka, M., Tsujimoto, M., Kunisada, M., Tada, S., Bito, T., Nishigori. C.
  • Journal Title: European Journal of Dermatology Volume: 22 Pages: 136-137
  • Peer Reviewed
• [Journal Article] Peristomal skin ulcer with intestinal metaplasia (2012)
  • Author(s): Ono, R., Oka, M., Sakaguchi, M., Nishioka, E., Kawakami, F., Nagano, T., Kunisada, M., Nishigori, C.
  • Journal Title: British Journal of Dermatology Volume: -
  • Peer Reviewed
• [Journal Article] Drug fever due to S-carboxymethyl-L-cysteine : The demonstrati on of a causative agent with patch tests (2011)
  • Author(s): Hatakeyama M, Fukunaga A, Shimizu H, Oka M, Horikawa T, Nishigori C
  • Journal Title: J Dermatol Volume: (Epub ahead of print) Issue: 6 Pages: 555-556
  • DOI: 10.1111/j.1346-8138.2011.01325.x
  • Peer Reviewed
• [Journal Article] Phospholipase Cε has a crucial role in ultraviolet B-induced neutrophil-associated skin inflammation by regulating the expression of CXCL1/KC (2011)
  • Author(s): Oka, M., Edamatsu, H., et al
  • Journal Title: Lab.Invest. Volume: 91 Issue: 5 Pages: 711-718
  • DOI: 10.1038/labinvest.2011.10
  • Peer Reviewed
• [Journal Article] Overexpression of phospholipase Cεin keratinocytes upregulates cytokine expression and causes dermatitis with acanthosis and T-cell infiltration (2011)
  • Author(s): Takenaka, N., Edamatsu, H., Suzuki, N., Saito, H., Inoue, Y., Oka, M., Hu, L., Kataoka T.
  • Journal Title: Eur. J. Immunol. Volume: 41(1) Issue: 1 Pages: 202-213
  • DOI: 10.1002/eji.201040675
  • Peer Reviewed
• [Journal Article] Primary cutaneous small cell carcinoma of the vulva arising from squamous cell carcinoma (2011)
  • Author(s): Matsumoto R, Bito T, Washio K, Ikeda T, Oka M, Manabe T, Nishigori C
  • Journal Title: Br J Dermatol Volume: 165 Issue: 5 Pages: 1147-1148
  • DOI: 10.1111/j.1365-2133.2011.10451.x
  • Peer Reviewed
• [Journal Article] Eccrine angiomatous hamartoma with sudden enlargement and pain in an adolescent girl after menarche (2011)
  • Author(s): Kikusawa, A., Oka, M., Taguchi, K., Shimizu, H., Kunisada, M., Nishigori, C.
  • Journal Title: Dermatoendocrinol Volume: 3(4) Issue: 4 Pages: 266-268
  • DOI: 10.4161/derm.3.4.15365
  • Peer Reviewed
• [Journal Article] Lipomatous vatiant of eccrine angiomatous hamartoma (2011)
  • Author(s): Kyo, A., Oka, M., Hiromoto, A., Kunisada, M., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 21(5) Issue: 5 Pages: 803-804
  • DOI: 10.1684/ejd.2011.1463
  • Peer Reviewed
• [Journal Article] Urticariform striae distensae with severe pruritus and pain in an obese woman (2011)
  • Author(s): Kanata, M., Oka, M., Nagai, H., Kunisada, M., Nishigori, C.
  • Journal Title: Eur. J. Dermatol. Volume: 21(5) Issue: 5 Pages: 799-800
  • DOI: 10.1684/ejd.2011.1456
  • Peer Reviewed
• [Journal Article] Rapid Desensitization with Autologous Sweat in Cholinergic Urticaria (2011)
  • Author(s): Kozaru, T., Fukunaga, A., Taguchi, K., Ogura, K., Nagano, T., Oka, M., Horikawa, T., Nishigori, C.
  • Journal Title: Allergology International Volume: 60 Issue: 3 Pages: 277-281
  • DOI: 10.2332/allergolint.10-OA-0269
  • NAID: 130004723038
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Urticariform striae distensae with severe pruritus and pain in an obese woman (2011)
  • Author(s): Mami Kanata, Masahiro Oka, Hiroshi Nagai, Makoto Kunisada, and Chikako Nishigori
  • Journal Title: European Journal of Dermatology Volume: 21 Pages: 799-800
  • Peer Reviewed
• [Journal Article] Lipomatous vatiant of eccrine angiomatous hamartoma (2011)
  • Author(s): Kyo, A., Oka, M., Hiromoto, A., Kunisada, M., Nishigori, C.
  • Journal Title: European Journal of Dermatology Volume: 21 Pages: 803-804
  • Peer Reviewed
• [Journal Article] Multiple apocrine poromas : A new case report
  • Author(s): Nishioka, M., Kunisada, M., Fujiwara, N., Oka, M., Funasaka, Y., Nishigori, C.
  • Journal Title: J. Cutan. Pathol. Volume: (in press)
  • Peer Reviewed
• [Presentation] Clinical and histopathological features of IgG4-related skin manifestations in patients with IgG4-related disease (2013)
  • Author(s): Masahiro Oka, Tetsuya Ikeda, Hideki Shimizu, Mayumi Hatakeyama,Haruhisa Kanki, Makoto Kunisada, Goh Tsuji, Akio Morinobu, Shunichi Kumagai,Atsushi Azumi, Akira Negi, Chikako Nishigori
  • Organizer: International Investigative Dermatology Meeting
  • Place of Presentation: エジンバラ(スコットランド)
• [Presentation] Role and regulation of STAT3 phosphorylation at Ser727 in in melanocytes and melanoma cells (2012)
  • Author(s): Masanobu Sakaguchi, Masahiro Oka, Tetsushi Iwasaki,Yasuo Fukami, Chikako Nishigori
  • Organizer: 2012 SID Annual Meeting & 75th Anniversary Celebration
  • Place of Presentation: Raleigh(アメリカ)
  • Year and Date: 2012-05-09
• [Presentation] 乾癬患者におけるアダリムマブまたはインフリキシマブの中和抗体と治療効果に対する検討 (2012)
  • Author(s): 西川里香、尾藤利憲、畠山真弓、菊澤亜夕子、神吉晴久、永井宏、岡昌宏、錦織千佳子、池田哲哉、堀川達弥、足立厚子、皿山泰子、吉崎仁胤、瀬戸英伸
  • Organizer: 第63回日本皮膚科学会中部支部学術大会
  • Place of Presentation: 大阪市
• [Presentation] Ser727 phosphorylation in STAT3 plays a crucial role in nuclear translocation of STAT3 and growth in human melanoma cells and melanocytes (2011)
  • Author(s): Masanobu Sakaguchi, Masahiro Oka, Tetsushi Iwasaki,Yasuo Fukami, Chikako Nishigori
  • Organizer: 21st International Pigment Cell Conference1
  • Place of Presentation: ボルドー(フランス)
• [Presentation] 尋常性乾癬患者におけるアダリブマブ中和抗体の出現と治療効果に対する検討 (2011)
  • Author(s): 菊澤亜夕子、尾藤利憲、永井宏、岡昌宏、錦織千佳子、大野健太郎、長野徹、堀川達弥、吉崎仁胤、神吉晴久
  • Organizer: 第62回日本皮膚科学会中部支部学術大会
  • Place of Presentation: 日津市
• [Presentation] Erythem elevatum diutinum on the legs associated with intractable skin ulcer on the back due to Koebner phenomenon (2011)
  • Author(s): Akane Furumatsu, Toshinori Bito, Masahiro Oka, Chikako Nishigori
  • Organizer: 日本研究皮膚科学会第36回年次学術大会
  • Place of Presentation: 京都市
• [Presentation] Ser727 phosphorylation in STAT3 plays a crucial role in nuclear translocation of STAT3 and growth in human melanoma cells and melanocytes (2011)
  • Author(s): Sakaguchi M., Oka M, Iwasaki T, Fukami Y, Nishigori C
  • Organizer: XXIst International Pigment Cell Conference
  • Place of Presentation: ボルドー（フランス）
• [Presentation] Erythema elevatum diutinum on the legs associated with intractable skin ulcer on the back due to Koebner phenomenon (2011)
  • Author(s): Furumatsu A, Bito T, Oka M, Nishigori C
  • Organizer: The 36th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 京都
• [Presentation] Role and regulation of STAT3 phosphorylation at Tyr705 and Ser727 in melanocytes and melanoma cells.
  • Author(s): Masahiro Oka
  • Organizer: The Wistar Institute Special Seminar
  • Place of Presentation: The Wistar Institute （USA）
  • Invited
• [Presentation] Tyr705 phosphorylation and Ser727 phosphorylation in STAT3 have their own roles and regulation mechanisms in melanocytes and melanoma cells.
  • Author(s): Masahiro Oka, Masanobu Sakaguchi, Takeshi Fukumoto, Tetsishi Iwasaki, Yasuo Fukami, Chikako Nishigori
  • Organizer: 第24回日本色素細胞学会学術大会：ワークショップ
  • Place of Presentation: 長浜バイオ大学（滋賀県）
  • Invited
• [Presentation] 乾癬の病態と抗TNF-α 製剤による治療経験
  • Author(s): 岡 昌宏
  • Organizer: 明石・西神戸乾癬治療病診連携の会
  • Place of Presentation: グリーンヒルホテル明石（兵庫県）
  • Invited
• [Presentation] 病診連携と乾癬研究
  • Author(s): 岡 昌宏
  • Organizer: 神戸乾癬治療病診連携の会
  • Place of Presentation: 神戸メリケンパークオリエンタルホテル（兵庫県）
  • Invited