線維化におけるＴＧＦ－β情報伝達の関与についての分子基盤の解明

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24591658
• Research Institution: Kumamoto University
• Principal Investigator: 尹 浩信 熊本大学, 生命科学研究部, 教授 (20282634)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 遺伝子 / 細胞・組織 / シグナル伝達

Outline of Annual Research Achievements

全身性強皮症、肺線維症の組織および病変部の培養線維芽細胞においてDNA microarry法にて過剰発現する分子、発現低下する分子を検討し、またrealtime PCRを用いたmicro RNA arrayによって過剰発現するmicro RNA、発現低下するmicro RNAを同定した。
正常皮膚線維芽細胞を用いてintegrinαVβ5 stable transfectant作成し、integrin αVβ5の過剰発現を確認した。
COL1A2 enhancer、promoterをベクターに組み込んで作成したtransgeneを用いて線維芽細胞特異的integrin αVβ5 transgenic mouseを作成し、phenotypeを解析したが、予想に反して皮膚の線維化は認められず、正常マウスと比較して皮膚厚の減少を認めた。
integrin αVβ5 stable transfectantを用いてDNA microarry法、realtime PCRを用いたmicro RNA array法、情報伝達protein arrayを行い、線維化phenotypeを形成しているか、すなわちTGF-β受容体が過剰発現しているか、TGF-β情報伝達経路（Smad2、Smad 3、Smad4、p300/CBP、p38 MAPK、PI3 kinase）が過剰リン酸化しているか、I型コラーゲンをはじめとする細胞外マトリックス蛋白および遺伝子が過剰発現しているか、MMP-1などのproteaseの発現が低下しているか、TIMP-1などのprotease inhibitorの発現が亢進しているか詳細に検討し、autocrine TGF-β signalingによりI型コラーゲンをはじめとする細胞外マトリックス蛋白および遺伝子が過剰発現し、MMP-1などのproteaseの発現が低下していることを確認した。

Research Products

• [Journal Article] Fascia lata onlay patch for repairing infected incisional hernias. (2015)
  • Author(s): Miyamoto Y, Watanabe M, Ishimoto T, Baba Y, Iwagami S, Sakamoto Y, Yoshida N, Masuguchi S, Ihn H, Baba H.
  • Journal Title: Surg Today Volume: 45 Pages: 121-124
  • Peer Reviewed
• [Journal Article] Hair shaft microRNA-221 levels as a new tumor marker of malignant melanoma. (2015)
  • Author(s): Inada T, Fukushima S, Murai M, Jinnin M, Miyashita A, Nakahara S, Yamashita J, Aoi J, Msuguchi S, Ihn H.
  • Journal Title: J Dermatol Volume: 42 Pages: 198-201
  • Peer Reviewed
• [Journal Article] Analysis of expression pattern of serum microRNA levels in patients with psoriasis (2014)
  • Author(s): Yusaku Koga; Masatoshi Jinnin; Asako Ichihara; Akihiko Fujisawa; Chikako Moriya; Keisuke Sakai; Satoshi Fukushima; Yuji Inoue; Hironobu Ihn
  • Journal Title: Journal of Dermatological Science Volume: 27 Pages: 170-171
  • Peer Reviewed
• [Journal Article] Association of linear IgA bullous disease with ulcerative colitis: A case of successful treatment with infliximab (2014)
  • Author(s): S. Yamada; T. Makino; M. Jinnin; K. Sakai; S. Fukushima; Y. Inoue; H. Ihn
  • Journal Title: Dermatology Volume: 4 Pages: 295-298
  • Peer Reviewed
• [Journal Article] Dots/globules on dermoscopy in nail-apparatus melanoma (2014)
  • Author(s): Yuji Inoue; Scott W. Menzies; Satoshi Fukushima; Hazuki Nishi-Kogushi; Azusa Miyashita; Shinichi Masukuchi; Faith Muchemwa; Toshiro Kageshita; Hironobu Ihn
  • Journal Title: International Journal of Dermatology Volume: 53 Pages: 88-92
  • Peer Reviewed
• [Journal Article] miR-205 down-regulation promotes proliferation of dermatofibrosarcoma protuberans tumor cells by regulating LRP-1 and ERK phosphorylation (2014)
  • Author(s): Ikko Kajihara; Masatoshi Jinnin; Miho Harada; Katsunari Makino; Noritoshi Honda; Takamitsu Makino; Toshikatsu Igata; Shinichi Masuguchi; Satoshi Fukushima; Hironobu Ihn
  • Journal Title: Archives of Dermatological Research Pages: 1-8
  • Peer Reviewed
• [Journal Article] Phase II study of i.v. interferon-gamma in Japanese patients with mycosis fungoides (2014)
  • Author(s): Makoto Sugaya; Yoshiki Tokura; Toshihisa Hamada; Ryoji Tsuboi; Yoichi Moroi; Takeshi Nakahara; Masahiro Amano; Syuichi Ishida; Daisuke Watanabe; Mamori Tani; Hironobu Ihn; Jun Aoi; Keiji
  • Journal Title: Journal of Dermatology Volume: 41 Pages: 50-56
  • Peer Reviewed
• [Journal Article] MIRSNP rs2910164 of miR-146a is associated with the muscle involvement in polymyositis/dermatomyositis (2014)
  • Author(s): Yoshifumi Okada; Masatoshi Jinnin; Takamitsu Makino; Ikko Kajihara; Katsunari Makino; Noritoshi Honda; Wakana Nakayama; Kuniko Inoue; Satoshi Fukushima; Hironobu Ihn
  • Journal Title: International Journal of Dermatology Volume: 53 Pages: 300-304
  • Peer Reviewed
• [Journal Article] Successful treatment of skin fistulas in systemic sclerosis patients with the combination of topical negative pressure therapy and split-thickness skin grafting (2014)
  • Author(s): Ikko Kajihara; Masatoshi Jinnin; Saori Yamada; Asako Ichihara; Takamitsu Makino; Toshikatsu Igata; Shinichi Masuguchi; Satoshi Fukushima; Hironobu Ihn
  • Journal Title: Modern Rheumatology Volume: 24 Pages: 374-376
  • Peer Reviewed
• [Journal Article] Clinical evaluation of moisturizers with physiological analysis of stratum corneum TARC and TSLP. (2014)
  • Author(s): Fukushima S, Morita E, Tanioka M, Miyachi Y, Murakami Y, Matsunaka H, Ihn H.
  • Journal Title: J Cosmetics, Dermatological Sciences and Applications Volume: 4 Pages: 37-43
  • Peer Reviewed
• [Journal Article] Serum adhesion molecule levels as prognostic markers in patients with early systemic sclerosis: a multicenter, prospective, observational study. (2014)
  • Author(s): Hasegawa M, Asano Y, Endo H, Fujimoto M, Goto D, Ihn H, Inoue K, Ishikawa O, Kawaguchi Y, Kuwana M, Ogawa F, Takahashi H, Tanaka S, Sato S, Takehara K.
  • Journal Title: PLoS One Volume: 9 Pages: e88150-e88150
  • Peer Reviewed
• [Journal Article] Angiopoietin-like protein 2 accelerates carcinogenesis by activating chronic inflammation and oxidative stress. (2014)
  • Author(s): Aoi J, Endo M, Kadomatsu T, Miyata K, Ogata A, Horiguchi H, Odagiri H, Matsuda T, Fukushima S, Jinnin M, Hirakawa S, Sawa T, Akaike T, Ihn H, Oike Y.
  • Journal Title: Mol Cancer Res Volume: 12 Pages: 239-247
  • Peer Reviewed
• [Journal Article] A case of psoriasis accompanied by arthritis after delivery. (2014)
  • Author(s): Kanemaru H, Jinnin M, Asao A, Ichihara A, Makino K, Kajihara I, Fujisawa A, Fukushima S, Ihn H.
  • Journal Title: BioScience Trends Volume: 8 Pages: 64-67
  • Peer Reviewed
• [Journal Article] Case of Fusarium paronychia successfully treated with occulisive dressing of antifungal cream. (2014)
  • Author(s): Ikeda I, Ohno T, Ohno H, Miyazaki Y, Nishimoto K, Makino T, Ihn H.
  • Journal Title: J Dermatol Volume: 41 Pages: 340-342
  • Peer Reviewed
• [Journal Article] Up-regulation of miR-18a contributes to the epidermal necrolysis in severe drug eruptions. (2014)
  • Author(s): Ichihara A, Wang Z, Jinnin M, Izono Y, Shimozono N, Yamane K, Fujisawa A, Moriya C, Fukushima S, Inoue Y, Ihn H.
  • Journal Title: J Allergy Clin Immunol Volume: 133 Pages: 1065-1074
  • Peer Reviewed
• [Journal Article] Effects of the immunosuppressant rapamycin on the expression of human α2(I) collagen and matrix metalloproteinase 1 genes in scleroderma dermal fibroblasts. (2014)
  • Author(s): Tamaki Z, Asano Y, Kubo M, Ihn H, Tada Y, Sugaya M, Kadono T, Sato S.
  • Journal Title: J Dermatol Sci Volume: 74 Pages: 251-259
  • Peer Reviewed
• [Journal Article] miR-424 levels in hair shaft are increased in psoriasis patients. (2014)
  • Author(s): Tsuru Y, Jinnin M, Ichihara A, Fujisawa A, Moriya C, Sakai K, Fukushima S, Ihn H
  • Journal Title: J Dermatol Volume: 41 Pages: 382-385
  • Peer Reviewed
• [Journal Article] Case of disseminated cutaneous Mycobacterium chelonae infection mimicking cutaneous vasculitis. (2014)
  • Author(s): Ichihara A, Jinnin M, Fukushima S, Inoue Y, Ihn H.
  • Journal Title: J Dermatol Volume: 41 Pages: 414-417
  • Peer Reviewed
• [Journal Article] Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerate cutaneous wound healing. (2014)
  • Author(s): Makino K, Jinnin M, Aoi J, Kajihara I, Makino T, Fukushima S, Sakai K, Nakayama K, Emoto N, Yanagisawa M, Ihn H.
  • Journal Title: PLoS One Volume: 9 Pages: e97972-e97972
  • Peer Reviewed
• [Journal Article] Decreased IL-20 expression in scleroderma skin contributes to cutaneous fibrosis. (2014)
  • Author(s): Kudo H, Jinnin M, Asano Y, Trojanowska M, Nakayama W, Inoue K, Honda N, Kajihara I, Makino K, Fukushima S, Ihn H.
  • Journal Title: Arthritis Rheumatol Volume: 65 Pages: 1636-1647
  • Peer Reviewed
• [Journal Article] Evaluation of sentinel node biopsy for cutaneous squamous cell carcinoma. (2014)
  • Author(s): Fukushima S, Masuguchi S, Igata T, Harada M, Aoi J, Miyashita A, Nakahara S, Inoue Y, Jinnin M, Shiraishi S, Yamashita Y, Ishihara T, Ihn H.
  • Journal Title: J Dermatol Volume: 41 Pages: 539-541
  • Peer Reviewed
• [Journal Article] Immunoglobulin G4-related disease in a psoriasis vulgaris patient treated with ustekinumab. (2014)
  • Author(s): Kajihara I, Makino K, Ichihara A, Fukushima S, Jinnin M, Hirooka S, Kojima K, Kourogi H, Ihn H.
  • Journal Title: J Dermatol Volume: 41 Pages: 670-671
  • Peer Reviewed
• [Journal Article] Serum levels of soluble carbonic anhydrase IX are decreased in patients with diffuse cutaneous systemic sclerosis compared to those with limited cutaneous systemic sclerosis. (2014)
  • Author(s): Makino K, Jinnin M, Makino T, Kajihara I, Fukushima S, Inoue Y, Ihn H.
  • Journal Title: Biosci Trends Volume: 8 Pages: 144-148
  • Peer Reviewed
• [Journal Article] Clincal significance of serum vascular endothelial-cadherin levels in inflammatory skin diseases. (2014)
  • Author(s): Kuriyama H, Jinnin M, Kanemaru H, Ichihara A, Fujisawa A, Moriya C, Fukushima S, Ihn H.
  • Journal Title: Ann Dermatol Volume: 26 Pages: 536-538
  • Peer Reviewed
• [Journal Article] Serum levels of matrix metalloproteinase-13 in patients with eosinophilic fasciitis. (2014)
  • Author(s): Asano Y, Ihn H, Jinnin M, Tamaki Z, Tamaki K, Sato S.
  • Journal Title: J Dermatol Volume: 41 Pages: 746-748
  • Peer Reviewed
• [Journal Article] The proportion of lymphocytic inflammation with CD123-positive cells in lupus erythematosus profundus predict a clinical response to treatment. (2014)
  • Author(s): Miyashita A, Fukushima S, Makino T, Yoshino Y, Yamashita J, Honda N, Aoi J, ,Ichihara A, Jinnin M, Inoue Y, Ihn H.
  • Journal Title: Acta Derm Venereol Volume: 94 Pages: 563-567
  • Peer Reviewed
• [Journal Article] Transcriptionally controlled tumor protein is a novel biologic target for neurofibromatosis type I (NF-1) -associated tumors. (2014)
  • Author(s): Kobayashi D, Hirayama M, Komohara Y, Mizuguchi S, Wilson Morifuji M, Ihn H, Takeya M, Kuramochi A, Araki N.
  • Journal Title: J Biol Chem Volume: 289 Pages: 26314-26326
  • Peer Reviewed
• [Journal Article] Down-regulation of microRNA-196a in the sera and involved skin of localized scleroderma patients. (2014)
  • Author(s): Makino T, Jinnin M, Etoh M, Yamane K, Kajihara I, Makino K, Ichihara A, Igata T, Sakai K, Fukushima S, Ihn H.
  • Journal Title: Eur J Dermatol Volume: 24 Pages: 470-476
  • Peer Reviewed
• [Journal Article] Serum levels of leptin receptor in patients with systemic sclerosis. (2014)
  • Author(s): Ohyoshi Y, Makino T, Jinnin M, Nakayama W, Fukushima S, Inoue Y, Ihn H.
  • Journal Title: Intractable Rare Dis Res Volume: 2 Pages: 55-58
  • Peer Reviewed
• [Journal Article] A simple and effective reconstructive technique for repairing defects of the upper lip using a hatchet flap. (2014)
  • Author(s): Aoi J, Nagatomo E, Masuguchi S, Fukushima S, Jinnin M, Ihn H.
  • Journal Title: J Dermatol Volume: 41 Pages: 1025-1026
  • Peer Reviewed
• [Journal Article] A case of anaplastic large cell lymphoma of skeletal muscle. (2014)
  • Author(s): Kubo Y, Jono T, Makino T, Sakai K, Masuguchi S, Fukushima S, Jinnin, Inoue Y, Ihn H.
  • Journal Title: J Dermatol Volume: 41 Pages: 999-1002
  • Peer Reviewed
• [Journal Article] Aesthethic reconstruction of defects in the lateral side wall of the nose using a local V-Y flap. (2014)
  • Author(s): Aoi J, Masuguchi S, Fukushima S, Jinnin M, Ihn H.
  • Journal Title: J Dermatol Volume: 41 Pages: 1026-1028
  • Peer Reviewed
• [Journal Article] Increased CCL22 expression in psoriatic skin predicts a good response to infliximab therapy. (2014)
  • Author(s): Kusumoto S, Kajihara I, Nagatomo E, Makino K, Ichihara A, Aoi J, Johno T, Makino T, Fukushima S, Jinnin M, Ihn H.
  • Journal Title: Br J Dermatol Volume: 171 Pages: 1259-1261
  • Peer Reviewed
• [Journal Article] The expression profile of the toll-like receptor family in scleroderma dermal fibroblasts. (2014)
  • Author(s): Sakoguchi A, Nakayama W, Jinnin M, Wang Z, Yamane K, Aoi J, Makino K, Kajihara I, Ichihara A, Makino T, Fukushima S, Sakai K, Inoue Y, Ihn H.
  • Journal Title: Clin Exp Rheumatol Volume: 32 Pages: S4-S9
• [Journal Article] Tsukushi is involved in the wound healing by regulating the expression of cytokines and growth factors. (2014)
  • Author(s): Niimori D, Kawano R, Niimori-Kita K, Ihn H, Ohta K.
  • Journal Title: J Cell Commun Signal Volume: 8 Pages: 173-177
  • Peer Reviewed
• [Journal Article] Clinical features of 80 cases with tinea faciei treated at a rural clinic in Japana. (2014)
  • Author(s): Noguchi H, Jinnin M, Miyata K, Hiruma M, Ihn H.
  • Journal Title: Drug Discov Ther Volume: 8 Pages: 245-248
  • Peer Reviewed
• [Presentation] Identification of disease-specific molecules in the skin of dermatomyositis and lupus erythematosus by proteomics analysis using LC-MS/MS. (2014)
  • Author(s): Nakamura K, Jinnin M, Fukushima S, Ihn H.
  • Organizer: 39 th Annual Meting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Osaka
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] Serum leptin receptor as a tumor marker of melanoma. (2014)
  • Author(s): Fukushima S, Mizutani H, Miyashita A, Yamashita J, Nakahara S, Jinnin M, Ihn H.
  • Organizer: 39 th Annual Meting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Osaka
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] Decreased IL-20 expression in scleroderma skin contributes to cutaneous fibrosis. (2014)
  • Author(s): Kudo H, Jinnin M, Ihn H.
  • Organizer: 39 th Annual Meting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Osaka
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] Search for the skin constancy maintenance factor using the proteomics method. . (2014)
  • Author(s): Niimori D, Niimori K, Ihn H.
  • Organizer: 39 th Annual Meting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Osaka
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] Down-regulation of microRNA-196a in the sera and involved skin of localized scleroderma patients. (2014)
  • Author(s): Makino T, Jinnin M, Etoh M, Yamane K, Kajihara I, Makino K, Ichihara A, Igata T, Sakai K, Fukushima S, Ihn H.
  • Organizer: ACR
  • Place of Presentation: Boston
  • Year and Date: 2014-11-14 – 2014-11-19
• [Presentation] Potential use of polysaccharide as a skin care material for atopic dermatitis. (2014)
  • Author(s): Tanaka T, Tanida Y, Hayashi T, Motoyama K, Higashi T, Kaneko S, Ishitsuka Y, Irie T, Kaneko T, Okajima M, Ihn H, Arima H.
  • Organizer: International Federation of Societies of Cosmetic Chemists in Paris
  • Place of Presentation: Paris
  • Year and Date: 2014-10-27 – 2014-10-30
• [Presentation] Decreased IL-20 expression in scleroderma skin contributes to cutaneous fibrosis. (2014)
  • Author(s): Kudo H, Jinnin M, Ihn H.
  • Organizer: 2014 Montaguna Symposium on the biology of skin
  • Place of Presentation: Oregon U.S.A.
  • Year and Date: 2014-10-09 – 2014-10-13
• [Presentation] Immunothrapy with human iPS-cell derived myeloid cell lines producing type I interferons against metastatic melanoma. (2014)
  • Author(s): Miyashita A, Fukushima S, Nakahara S, Yamashita J, Senju S, Nishimura Y, Jinnin M, Ihn H.
  • Organizer: 44 th ESDR
  • Place of Presentation: Copenhagen
  • Year and Date: 2014-09-10 – 2014-09-13
• [Presentation] Serum levels of leptin receptor as a new tumor marker of malignant melanoma. (2014)
  • Author(s): Fukushima S, Mizutani H, Miyashita A, Yamashita J, Nakahara S, Jinnin M, Ihn H.
  • Organizer: 44 th ESDR
  • Place of Presentation: Copenhagen
  • Year and Date: 2014-09-10 – 2014-09-13
• [Presentation] Tsukushi controls the hair cycle by regulating TGF-β1 signaling. (2014)
  • Author(s): Niimori D, Fukushima S, Miyashita A, Ihn H.
  • Organizer: 44 th ESDR
  • Place of Presentation: Copenhagen
  • Year and Date: 2014-09-10 – 2014-09-13
• [Presentation] Sentinel node biopsy for non-melanoma skin cancers: A review of 88 cases at one institution. (2014)
  • Author(s): Fukushima S, Ihn H.
  • Organizer: 第11回日独皮膚科学会
  • Place of Presentation: ハイデルベルグ
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] Clinical significance of cobble stone appearance on the skin of patients with systemic sclerosis. (2014)
  • Author(s): Sawamura S, Kajihara I, Fukushima S, Ihn H.
  • Organizer: 第11回日独皮膚科学会
  • Place of Presentation: ハイデルベルグ
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] Successful treatment of skin fistulas in systemic sclerosis patients with the combination of topical negative pressure therapy and split-thickness skin grafting. (2014)
  • Author(s): Watanabe C, Kajihara I, Fukushima S, Ihn H.
  • Organizer: 第11回日独皮膚科学会
  • Place of Presentation: ハイデルベルグ
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] Clinical signaificance of CD169-positive lymph node macrophages in human malignant tumors. (2014)
  • Author(s): Ohnishi K, Saito Y, Komohara Y, Miyamoto Y, Fukushima S, Yamaguchi M, Baba H, Ihn H, Katabuchi H, Takeya M.
  • Organizer: 第50回米国癌治療学会議（ASCO2014）
  • Place of Presentation: シカゴ
  • Year and Date: 2014-05-30 – 2014-06-03