possibilityof new therapeutic agent for systemic screlosis by anti-CTGF antibody

• Project/Area Number: 18K08415
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Juntendo University
• Principal Investigator: Morimoto Shinji 順天堂大学, 医学部, 教授 (00348947)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 強皮症 / 坑CTGF抗体 / 坑線維化 / 間質性肺炎 / 皮膚硬化 / 炎症性サイトカイン / 抗線維化 / 全身性強皮症 / 抗体製剤 / 生物学的製剤 / インターロイキン17 / 抗CTGF抗体 / 分子標的薬 / CTGF

Outline of Final Research Achievements

Systemic sclerosis (SSc) is known to be refractory disease due to fibrosis of the skin and internal organs. Although connective tissue growth factor (CTGF) has been well-documented in SSc fibrosis, CTGF has not been fully investigated. We studied the effects of Anti-CTGF antibody in SSc mice model. We examined pulmonary fibrosis and skin fibrosis in the mice model. Dermal sclerosis, pulmonary fibrosis and cytokine production were assessed. As for skin and pulmonary fibrosis in the topoisomeraseⅠ mice model, there were no statistically significant difference in the treatment with anti-CTGF antibody, but it had tendency to mitigate both fibrosis. In terms of fibrotic cytokine, SPP1 and α smooth muscle actin (ACTA2) had tendency to be reduced by treatment with anti-CTGF antibody. Anti-CTGF antibody may have anti-fibrotic effects in mice models of systemic sclerosis. Further researches are required to evaluate it.

Academic Significance and Societal Importance of the Research Achievements

CTGFはCCN familyに属する成長因子であり、皮膚、心臓、肺、肝臓や腎臓を含む多臓器の線維化のhallmarkであり、CTGFを標的とした抗線維化薬はSScの主要病変の皮膚硬化を改善するのみならず、間質性肺炎、肺高血圧症、強皮症腎ならびに腸管の線維化等の重篤な内臓合併症を抗CTGF抗体で同時に改善することが我々の研究結果から予測されることが研究成果の学術的意義である。またSScの根源的病因である線維化を抗CTGF抗体投与にて抑制することにより、SScの生命予後の改善を期待できることが社会的意義である。

Research Products

• [Journal Article] Exposure of female NZBWF1 mice to imiquimod-induced lupus nephritis at an early age via a unique mechanism that differed from spontaneous onset (2022)
  • Author(s): Hayakawa Kunihiro、Fujishiro Maki、Yoshida Yuko、Kataoka Yuko、Sakuma Shota、Nishi Takuya、Ikeda Keigo、Morimoto Shinji、Takamori Kenji、Sekigawa Iwao
  • Journal Title: Clinical and Experimental Immunology Volume: uxac012 Issue: 1 Pages: 33-46
  • DOI: 10.1093/cei/uxac012
  • Peer Reviewed / Open Access
• [Journal Article] Social defeat stress exacerbates atopic dermatitis through downregulation of DNA methyltransferase 1 and upregulation of C?C motif chemokine receptor 7 in skin dendritic cells (2020)
  • Author(s): Yoshida Yuko、Hayakawa Kunihiro、Fujishiro Maki、Ikeda Keigo、Tsushima Hiroshi、Hirai Takuya、Kawasaki Mikiko、Tominaga Mitsutoshi、Suga Yasushi、Takamori Kenji、Watanabe Yoshifumi、Sekigawa Iwao、Morimoto Shinji
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 529 Issue: 4 Pages: 1073-1079
  • DOI: 10.1016/j.bbrc.2020.06.157
  • Peer Reviewed
• [Journal Article] MicroRNA-766-3p Contributes to Anti-Inflammatory Responses through the Indirect Inhibition of NF-κB Signaling (2019)
  • Author(s): Hayakawa Kunihiro、Kawasaki Mikiko、Hirai Takuya、Yoshida Yuko、Tsushima Hiroshi、Fujishiro Maki、Ikeda Keigo、Morimoto Shinji、Takamori Kenji、Sekigawa Iwao
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 4 Pages: 809-809
  • DOI: 10.3390/ijms20040809
  • Peer Reviewed / Open Access
• [Journal Article] A Case of MPO-ANCA Positive Systemic Lupus Erythematosus Developed into Acute Kidney Injury (2019)
  • Author(s): Suzuki Satoshi、Ogiwara Kei、Nishi Takuya、Sakuma Shota、Akira Maiko、Iwasaki Masako、Honda Daisuke、Takahara Hisatsugu、Ikeda Keigo、Yamaji, Naoto Tamura Ken、Morimoto Shinji、Rinno Hisaki
  • Journal Title: Archives of Clinical and Medical Case Reports Volume: 03 Issue: 06 Pages: 560-566
  • DOI: 10.26502/acmcr.96550134
  • Peer Reviewed / Open Access
• [Journal Article] Connective Tissue Growth Factor Neutralization Aggravates the Psoriasis Skin Lesion: The Analysis of Psoriasis Model Mice and Patients (2018)
  • Author(s): Hayakawa Kunihiro、Ikeda Keigo、Fujishiro Maki、Yoshida Yuko、Hirai Takuya、Tsushima Hiroshi、Miyashita Tomoko、Morimoto Shinji、Suga Yasushi、Takamori Kenji、Ogawa Hideoki、Sekigawa Iwao
  • Journal Title: Annals of Dermatology Volume: 30 Issue: 1 Pages: 47-47
  • DOI: 10.5021/ad.2018.30.1.47
  • Peer Reviewed / Open Access
• [Journal Article] Securely collecting multidimensional health information from patients with rheumatoid arthritis using smart device technology: Beneficial effect for physicians and patients (2018)
  • Author(s): Ikeda Keigo、Sekiguchi Naoya、Hirai Takuya、Tanji Kana、Zushi Atsuko、Inoue Mayumi、Takasago Masayuki、Komatsu Takaaki、Morimoto Shinji、Yamaji Ken、Takamori Kenji、Tamura Naoto、Sekigawa Iwao
  • Journal Title: Musculoskeletal Care Volume: 16 Issue: 4 Pages: 494-499
  • DOI: 10.1002/msc.1354
  • Peer Reviewed
• [Journal Article] Aortic Aneurysm as a Complication of Granulomatosis with Polyangiitis Successfully Treated with Prednisolone and Cyclophosphamide: A Case Report and Review of the Literature (2018)
  • Author(s): Niimi Naoko、Miyashita Tomoko、Tanji Kana、Hirai Takuya、Watanabe Kozo、Ikeda Keigo、Morimoto Shinji、Sekigawa Iwao
  • Journal Title: Case Reports in Rheumatology Volume: - Pages: 1-6
  • DOI: 10.1155/2018/9682801
  • Peer Reviewed
• [Journal Article] Circulating plasma microRNA profiling in patients with polymyositis/dermatomyositis before and after treatment: miRNA may be associated with polymyositis/dermatomyositis (2018)
  • Author(s): Hirai Takuya、Ikeda Keigo、Tsushima Hiroshi、Fujishiro Maki、Hayakawa Kunihiro、Yoshida Yuko、Morimoto Shinji、Yamaji Ken、Takasaki Yoshinari、Takamori Kenji、Tamura Naoto、Sekigawa Iwao
  • Journal Title: Inflammation and Regeneration Volume: 38 Issue: 1 Pages: 1-9
  • DOI: 10.1186/s41232-017-0058-1
  • Peer Reviewed / Open Access
• [Presentation] 大型血管炎との鑑別を要したStreptococcus pseudopneumoniaeによる感染性解離性大動脈瘤について (2022)
  • Author(s): 谷口 ゆき乃, 鈴木 智, 中澤 武司, 大谷 友也, 池田 圭吾, 森本 真司
  • Organizer: 第682回日本内科学会関東地方会
• [Presentation] 末梢血細胞分画変動及びB細胞内シグナルへの影響から検証したベリムマブの役割 (2022)
  • Author(s): 西 卓也, 藤城 真樹, 早川 国宏, 鈴木 智, 池田 圭吾, 森本 真司, 山路 健, 田村 直人
  • Organizer: 第66回日本リウマチ学会総会・学術集会
• [Presentation] 全身性エリテマトーデス患者における生活の質、骨密度、睡眠時間に関する検討 順天堂SLE前向きレジストリ研究(JUMP study)より (2022)
  • Author(s): 松下 雅和, 小笠原 倫大, 多田 久里守, 草生 真規雄, 箕輪 健太郎, 安倍 能之, 塚原 隆伊, 森本 真司, 梁 広石, 天野 浩文, 野澤 和久, 松平 蘭, 片桐 彰, 山路 健, 田村 直人
  • Organizer: 第66回日本リウマチ学会総会・学術集会
• [Presentation] MPO-ANCA陽性でループス様症状と血管炎症状が混在した腎炎患者に関する検討 (2022)
  • Author(s): 野嶋 仁貴, 鈴木 智, 大谷 友也, 篠浦 まりな, 池田 圭吾, 山路 健, 田村 直人, 森本 真司
  • Organizer: 第66回日本リウマチ学会総会・学術集会
• [Presentation] 入院加療を要した成人発症Still病36例の臨床的特徴と治療成績の検討 (2022)
  • Author(s): 鈴木 智, 篠浦 まりな, 大谷 友也, 池田 圭吾, 山路 健, 田村 直人, 森本 真司
  • Organizer: 第66回日本リウマチ学会総会・学術集会
• [Presentation] 長期経過で複数回の間質性肺炎増悪を来した抗MDA5抗体陽性CADM3例の臨床的検討 (2019)
  • Author(s): 鈴木 智, 西 卓也, 作間 渉太, 池田 圭吾, 山路 健, 田村 直人, 森本 真司
  • Organizer: 第63回日本リウマチ学会総会・学術集会
• [Presentation] SLE治療過程におけるmiRNAの変動解析について (2018)
  • Author(s): 津島浩、森本 真司, 平井 琢也, 池田 圭吾, 山路 健, 関川 巖, 田村 直人
  • Organizer: 日本内科学会