Elucidation of CD147-mediated mechanism in renal energy metabolism

• Project/Area Number: 26461220
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nagoya University
• Principal Investigator: Kosugi Tomoki 名古屋大学, 医学部附属病院, 講師 (90584681)
• Co-Investigator(Kenkyū-buntansha): 丸山 彰一 名古屋大学, 医学系研究科, 教授 (10362253) ; 佐藤 和一 藤田保健衛生大学, 医学部, 准教授 (90508920) ; 林 宏樹 藤田保健衛生大学, 医学部, 助教 (10378086)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: CD147 / メタボリック症候群 / ATP産生 / 高脂肪食 / 脂肪肝

Outline of Final Research Achievements

CD147/Basigin, a glycosylated transmembrane protein, plays important roles of cell survival, invasion and metastasis. With regard to metabolic syndrome involving diabetes mellitus, kidney and liver dysfunction, however, the molecular mechanism involving CD147 remains unknown. CD 147 promotes lactate metabolism as a chaperone of Monocarboxylate transporter, and exerts a great influence on intracellular energy metabolism/ATP production. Oxidative stress caused by excessive intracellular accumulation of sugar, lipid and uric acid induces synergistic organ dysfunction by inducing CD 147 leading to the formation of a negative cycle. Therefore, the attention has become extended to obesity-related renal and liver dysfunction.

Research Products

• [Journal Article] Fructose and uric acid in diabetic nephropathy. (2015)
  • Author(s): Bjornstad P, Lanaspa MA, Ishimoto T, Kosugi T, Kume S, Jalal D, Maahs DM, Snell-Bergeon JK, Johnson RJ, Nakagawa T.
  • Journal Title: Diabetologia. Volume: 58 Issue: 9 Pages: 1993-2002
  • DOI: 10.1007/s00125-015-3650-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD147/Basigin limits lupus nephritis and TH17 cell differentiation by inhibiting the IL-6/STAT3 pathway. (2015)
  • Author(s): Maeda, K., T. Kosugi, W. Sato, H. Kojima, Y. Sato, D. Kamimura, N. Kato, N. Tsuboi, Y. Yuzawa, S. Matsuo, M. Murakami, S. Maruyama, K. Kadomatsu.
  • Journal Title: Arthritis Rheumatol. Volume: 印刷中 Issue: 8 Pages: 2185-2195
  • DOI: 10.1002/art.39155
  • Peer Reviewed / Open Access
• [Journal Article] Midkine Regulates BP through Cytochrome P450-Derived Eicosanoids. (2014)
  • Author(s): Sato Y, Sato W, Maruyama S, Wilcox CS, Falck JR, Masuda T, Kosugi T, Kojima H, Maeda K, Furuhashi K, Ando M, Imai E, Matsuo S, Kadomatsu
  • Journal Title: J Am Soc Nephrol. Volume: Epub
  • Peer Reviewed
• [Journal Article] Neutrophil/lymphocyte ratio as a predictor of cardiovascular events in incident dialysis patients: a Japanese prospective cohort study. (2014)
  • Author(s): Abe T, Kato S, Tsuruta Y, Sugiura S, Katsuno T, Kosugi T, Tsuboi N, Matsuo S, Maruyama S.
  • Journal Title: Clin Exp Nephrol Volume: Epub
  • Peer Reviewed
• [Journal Article] Patient age and the prognosis of idiopathic membranous nephropathy. (2014)
  • Author(s): Yamaguchi M, Ando M, Yamamoto R, Akiyama S, Kato S, Katsuno T, Kosugi T, Sato W, Tsuboi N, Yasuda Y, Mizuno M, Ito Y, Matsuo S, Maruyama S.
  • Journal Title: PLoS One Volume: 9(10) Issue: 10 Pages: 110376-110376
  • DOI: 10.1371/journal.pone.0110376
  • Peer Reviewed
• [Journal Article] Pristane-induced granulocyte recruitment promotes phenotypic conversion of macrophages and protects against diffuse pulmonary hemorrhage in Mac-1 deficiency. (2014)
  • Author(s): Shi Y, Tsuboi N, Furuhashi K, Du Q, Horinouchi A, Maeda K, Kosugi T, Matsuo S, Maruyama S.
  • Journal Title: J Immunol. Volume: 193 Issue: 10 Pages: 5129-39
  • DOI: 10.4049/jimmunol.1401051
  • Peer Reviewed
• [Journal Article] CD147 (EMMPRIN/Basigin) in kidney diseases: from an inflammation and immune system viewpoint. (2014)
  • Author(s): Kosugi T, Maeda K, Sato W, Maruyama S, Kadomatsu K.
  • Journal Title: Nephrol Dial Transplan Volume: Epub
  • Peer Reviewed
• [Journal Article] Smoking is a risk factor for the progression of idiopathic membranous nephropathy. (2014)
  • Author(s): Yamaguchi M, Ando M, Yamamoto R, Akiyama S, Kato S, Katsuno T, Kosugi T, Sato W, Tsuboi N, Yasuda Y, Mizuno M, Ito Y, Matsuo S, Maruyama S.
  • Journal Title: PLoS One. Volume: 9 Issue: 6 Pages: e100835-e100835
  • DOI: 10.1371/journal.pone.0100835
  • Peer Reviewed / Open Access
• [Journal Article] CD147/basigin reflects renal dysfunction in patients with acute kidney injury. (2014)
  • Author(s): Nagaya H, Kosugi T, Maeda-Hori M, Maeda K, Sato Y, Kojima H, Hayashi H, Kato N, Ishimoto T, Sato W, Yuzawa Y, Matsuo S, Kadomatsu K, Maruyama S.
  • Journal Title: Clin Exp Nephrol. Volume: 18 Issue: 5 Pages: 746-54
  • DOI: 10.1007/s10157-013-0916-3
  • Peer Reviewed
• [Journal Article] Comparison of kidney disease: improving global outcomes and acute kidney injury network criteria for assessing patients in intensive care units. (2014)
  • Author(s): Shinjo H, Sato W, Imai E, Kosugi T, Hayashi H, Nishimura K, Nishiwaki K, Yuzawa Y, Matsuo S, Maruyama S.
  • Journal Title: Clin Exp Nephrol Volume: 18(5) Issue: 5 Pages: 737-45
  • DOI: 10.1007/s10157-013-0915-4
  • Peer Reviewed
• [Presentation] CD147/Basigin Deficiency Prevents the Development of Podocyte Injury Through the Integrin/FAK Signaling Pathway. (2016)
  • Author(s): Tomoki Yoshioka, Tomoki Kosugi, Kayaho Maeda, Tomohiro Masuda, Yuka Sato, Hiroshi Kojima, Noritoshi Kato, Takuji Ishimoto, Shoichi Maruyama.
  • Organizer: 49th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Chicago,IL, USA
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] 尿蛋白出現機序におけるCD147/Basiginの役割 (2016)
  • Author(s): 吉岡 知輝、小杉 智規、森 佳子、前田 佳哉輔、門松 健治 (名古屋大学分子生物学)、松尾 清一、丸山 彰一
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-06-19
• [Presentation] CD147/bsg accelerates tubulointerstitial injury and liver dysfunction in high-fat diet. (2016)
  • Author(s): Yoshiko Mori, Tomoki Kosugi, Tomoki Yoshioka, Takahiro Hayasaki, Kayaho Maeda, Noritoshi Kato, Takuji Ishimoto, Seiichi Matsuo, Shoichi Maruyama.
  • Organizer: 53RD ERA-EDTA CONGRESS
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2016-05-23
  • Int'l Joint Research
• [Presentation] The role of basigin in the development of proteinuria. (2016)
  • Author(s): Tomoki Yoshioka1, Tomoki Kosugi1, Yoshiko Mori1, Kayaho Maeda2, Seiichi Matsuo1, Shoichi Maruyama1, 1Nagoya University Graduate School of Medicine, Nephrology, Nagoya-shi, Aichi-ken, JAPAN, 2Beth Israel Deaconess Medical Center, Harvard Medical School, Rheumatology, Boston, MA.
  • Organizer: 53RD ERA-EDTA CONGRESS
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2016-05-22
  • Int'l Joint Research
• [Presentation] CD147は虚血に伴う急性腎障害を反映する (2015)
  • Author(s): 小杉 智規、長屋 啓、前田 佳哉輔、増田 智広、加藤 規利、石本 卓嗣、坪井 直毅、松尾 清一、丸山 彰一
  • Organizer: 第60回日本透析医学会学術総会・集会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2015-06-26
• [Presentation] 腎疾患活動性マーカーとしてのCD147の有用性の検討 (2015)
  • Author(s): 小杉 智規、吉岡 知輝、増田 智広、前田 佳哉輔、加藤 規利、石本 卓嗣、坪井 直毅、松尾 清一、丸山 彰一
  • Organizer: 第60回日本透析医学会学術総会・集会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2015-06-26
• [Presentation] CD147はIL-17産生T細胞の分化を制御し、実験ループス腎炎の病勢を抑制する (2015)
  • Author(s): 前田 佳哉輔、小杉 智規、増田 智広、佐藤 由香、坪井 直毅、佐藤 和一、松尾 清一、丸山 彰一
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県、名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] 腎疾患活動性マーカーとしてのCD147の有用性の検討 (2015)
  • Author(s): 吉岡 知輝、小杉 智規、森 佳子、増田 智広、前田 佳哉輔、松尾 清一、丸山 彰一
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県、名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] The Growth Factor Midkine Reflect the Disease Activity in Lupus Nephritis (2014)
  • Author(s): Tomohiro Masuda, MD, Kayaho Maeda, MD, Waichi Sato, MD, PhD, Tomoki Kosugi, MD, PhD, Yuka Sato, MD, Takuji Ishimoto, MD, PhD, Seiichi Matsuo, MD, Shoichi Maruyama, MD.
  • Organizer: Kidney Week 2014
  • Place of Presentation: フィラデルフィア (米国)
  • Year and Date: 2014-11-11 – 2014-11-16
• [Presentation] Smoking Is a Risk Factor for the Relapse of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. (2014)
  • Author(s): Makoto Yamaguchi, MD, Sawako Kato, MD, PhD, Takuji Ishimoto, MD, PhD, Tomoki Kosugi, MD, PhD, Waichi Sato, MD, PhD, Naotake Tsuboi, MD, PhD, Masashi Mizuno, MD, PhD, Yasuhiko Ito, MD, PhD, Seiichi Matsuo, MD, Shoichi Maruyama, MD.
  • Organizer: Kidney Week 2014
  • Place of Presentation: フィラデルフィア (米国)
  • Year and Date: 2014-11-11 – 2014-11-16
• [Presentation] Plasma CD147/Basigin as a Promising Biomarker of the Kidney Diseases (2014)
  • Author(s): Kayaho Maeda, MD, Tomoki Kosugi, MD, PhD, Hiroshi Kojima, MD, Tomohiro Masuda, MD, Noritoshi Kato, MD, PhD, Waichi Sato, MD, PhD, Seiichi Matsuo, MD,
  • Organizer: Kidney Week 2014
  • Place of Presentation: フィラデルフィア (米国)
  • Year and Date: 2014-11-11 – 2014-11-16
• [Presentation] PRESの画像所見を呈し、血漿交換と免疫抑制治療が奏効したNP-SLEの一例 (2014)
  • Author(s): 伊藤 一洸、田中 章仁、勝野 敬之、加藤 規利、鈴木 康弘、加藤 佐和子、石本 卓嗣、尾崎 武徳、小杉 智規、安田 宣成、佐藤 和一、坪井 直毅、水野 正司、伊藤 恭彦、丸山 彰一、松尾 清一
  • Organizer: 第44回日本腎臓学会西部学術大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] 筋痛症状を呈し、CAPD継続が危惧されたPMRの2症例 (2014)
  • Author(s): 小崎 陽平、鈴木 康弘、坂田 史子、加藤 規利、勝野 敬之、石本 卓嗣、小杉 智規、佐藤 和一、坪井 直毅、水野 正司、丸山 彰一、伊藤 恭彦、松尾 清一
  • Organizer: 第44回日本腎臓学会西部学術大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] 生体腎移植後に発症したPost-transplant lymphoproliferative disease (PTLD)の一例 (2014)
  • Author(s): 酒井 尊之、鈴木 康弘、坂田 史子、加藤 規利、勝野 敬之、石本 卓嗣、小杉 智規、佐藤 和一、坪井 直毅、水野 正司、丸山 彰一、伊藤 恭彦、松尾 清一
  • Organizer: 第44回日本腎臓学会西部学術大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] CD147/basiginは急性期の腎機能障害を反映する (2014)
  • Author(s): 長屋 啓、小杉 智規、小島 博、前田 佳哉輔、加藤 規利、石本 卓嗣、飯田 喜康、佐藤 和一、松尾 清一、丸山 彰一
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 透析導入時の血清マグネシウム値と背景因子の関連についての検討 (2014)
  • Author(s): 田中 章仁、加藤 規利、勝野 敬之、尾崎 武徳、加藤 佐和子、小杉 智規、佐藤 和一、坪井 直毅、丸山 彰一、稲熊 大城、松尾 清一
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 喫煙と特発性膜性腎症の腎予後との関連性について (2014)
  • Author(s): 山口 真、安藤 昌彦、秋山 真一、加藤 佐和子、勝野 敬之、小杉 智規、佐藤 和一、坪井 直毅、安田 宜成、水野 正司、伊藤 恭彦、松尾 清一、丸山 彰一
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 腹膜透析患者におけるC.E.R.A.投与量に関連する因子の検討 (2014)
  • Author(s): 鈴木 康弘、坂田 史子、勝野 敬之、加藤 規利、尾崎 武徳:、小杉 智規:、佐藤 和一、坪井 直毅、丸山 彰一、水野 正司、松尾 清一、伊藤 恭彦
  • Organizer: 第59回日本透析医学会学術総会・集会
  • Place of Presentation: 神戸ポートピアホテル （兵庫県神戸市）
  • Year and Date: 2014-06-12 – 2014-06-15
• [Presentation] 長期腹膜透析（PD）患者に生じた左房内calcified amorphous tumor（CAT）の1例 (2014)
  • Author(s): 田中 章仁、水野 正司、大島 英揮、筑紫 さおり、石川 英昭、坂田 史子、加藤 規利、鈴木 康弘、勝野 敬之、尾崎 武徳、小杉 智規、坪井 直毅、佐藤 和一、丸山 彰一、松尾 清一、伊藤 恭彦
  • Organizer: 第59回日本透析医学会学術総会・集会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2014-06-12 – 2014-06-15