脂質シャペロンが寄与する脂質代謝と腎臓病の発症及び進展機序の解明

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19K08708
• Research Institution: Sapporo Medical University
• Principal Investigator: 田中 希尚 札幌医科大学, 医学部, 研究員 (60533362)
• Co-Investigator(Kenkyū-buntansha): 古橋 眞人 札幌医科大学, 医学部, 講師 (20563852)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脂肪酸結合タンパク4 / 糸球体障害 / 糸球体内皮細胞 / 糸球体上皮細胞 / 尿バイオマーカー

Outline of Annual Research Achievements

腎生検症例の尿サンプルを用いた検討で、尿FABP4排泄量が尿中微量アルブミン量や尿蛋白量と正相関し、いずれも腎機能障害進行と関連することを報告した。一方、IgA腎症とその動物モデルであるgddYの腎組織解析及び血清・尿解析において、糸球体内FABP4発現量が尿蛋白量、血清FABP4濃度及び尿FABP4排泄量と強く相関することを見出した。更にin vitroでの検討において、ヒト糸球体内皮細胞 (HRGEC: Human Renal Glomerular Endothelial Cells)では血管内皮増殖因子 (VEGF) の刺激によりFABP4の発現と細胞外分泌が誘導されるのを確認し、HRGEC及び分化誘導したマウス糸球体上皮細胞MPC (Mouse Podocyte Clone)ではFABP4刺激によって炎症性サイトカインマーカーと小胞体ストレスマーカーの遺伝子発現が亢進することを確認した。以上よりFABP4は糸球体障害と深く関連することが明らかとなり、尿FABP4排泄量が新規糸球体障害のバイオマーカーとなる可能性が示唆された。

Research Products

• [Journal Article] Circulating level of fatty acid‐binding protein 4 is an independent predictor of metabolic dysfunction‐associated fatty liver disease in middle‐aged and elderly individuals (2022)
  • Author(s): Tanaka Marenao、Takahashi Satoko、Higashiura Yukimura、Sakai Akiko、Koyama Masayuki、Saitoh Shigeyuki、Shimamoto Kazuaki、Ohnishi Hirofumi、Furuhashi Masato
  • Journal Title: Journal of Diabetes Investigation Volume: Dec 9 Pages: -
  • DOI: 10.1111/jdi.13735
  • Peer Reviewed / Open Access
• [Journal Article] A case of membranous nephropathy secondary to asymptomatic Graves’ disease (2022)
  • Author(s): Moniwa Norihito、Shioya Yu、Gocho Yufu、Takahashi Satoko、Tanaka Marenao、Furuhashi Masato、Kuroda Setsuko、Hama Taketsugu、Shima Yuko、Ogawa Yayoi、Miura Tetsuji
  • Journal Title: CEN Case Reports Volume: Jan 6 Pages: -
  • DOI: 10.1007/s13730-021-00672-0
  • Peer Reviewed / Open Access
• [Journal Article] Diabetes modulation of the myocardial infarction-acute kidney injury axis (2022)
  • Author(s): Miura Tetsuji、Kuno Atsushi、Tanaka Marenao
  • Journal Title: American Journal of Physiology-Heart and Circulatory Physiology Volume: 322 Pages: H394～H405
  • DOI: 10.1152/ajpheart.00639.2021
  • Peer Reviewed
• [Journal Article] Plasma Tsukushi Concentration Is Associated with High Levels of Insulin and FGF21 and Low Level of Total Cholesterol in a General Population without Medication (2022)
  • Author(s): Furuhashi Masato、Higashiura Yukimura、Sakai Akiko、Koyama Masayuki、Tanaka Marenao、Saitoh Shigeyuki、Shimamoto Kazuaki、Ohnishi Hirofumi
  • Journal Title: Metabolites Volume: 12 Pages: 237～237
  • DOI: 10.3390/metabo12030237
  • Peer Reviewed / Open Access
• [Journal Article] High fibrosis-4 (FIB-4) index predicts new onset of ischemic heart disease during a 10-year period in a general population (2022)
  • Author(s): Higashiura Yukimura、Tanaka Marenao、Mori Kazuma、Mikami Takuma、Hosaka Itaru、Ohnishi Hirofumi、Hanawa Nagisa、Furuhashi Masato
  • Journal Title: European Heart Journal Open Volume: - Pages: -
  • DOI: 10.1093/ehjopen/oeac030
  • Peer Reviewed / Open Access
• [Journal Article] Reply to the comments of Naharci on “Circulating level of fatty acid‐binding protein?4 is an independent predictor of metabolic dysfunction‐associated fatty liver disease in middle‐aged and elderly individuals” (2022)
  • Author(s): Tanaka Marenao、Furuhashi Masato
  • Journal Title: Journal of Diabetes Investigation Volume: 13 Pages: 928～929
  • DOI: 10.1111/jdi.13808
  • Peer Reviewed / Open Access
• [Journal Article] Increased LDL cholesterol level is associated with deterioration of renal function in males (2022)
  • Author(s): Osanami Arata、Tanaka Marenao、Furuhashi Masato、Ohnishi Hirofumi、Hanawa Nagisa、Yamashita Tomohisa、Moniwa Norihito、Miura Tetsuji
  • Journal Title: Clinical Kidney Journal Volume: - Pages: -
  • DOI: 10.1093/ckj/sfac111
  • Peer Reviewed / Open Access
• [Journal Article] Elevated circulating FABP4 concentration predicts cardiovascular death in a general population: a 12-year prospective study (2021)
  • Author(s): Saito Norie、Furuhashi Masato、Koyama Masayuki、Higashiura Yukimura、Akasaka Hiroshi、Tanaka Marenao、Moniwa Norihito、Ohnishi Hirofumi、Saitoh Shigeyuki、Ura Nobuyuki、Shimamoto Kazuaki、Miura Tetsuji
  • Journal Title: Scientific Reports Volume: 11 Pages: 4008
  • DOI: 10.1038/s41598-021-83494-5
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of necroptosis in contrast-induced nephropathy in a rat CKD model (2021)
  • Author(s): Shibata Satoru、Moniwa Norihito、Kuno Atsushi、Kimura Ayumu、Ohwada Wataru、Sugawara Hirohito、Gocho Yufu、Tanaka Marenao、Yano Toshiyuki、Furuhashi Masato、Tanno Masaya、Miki Takayuki、Miura Tetsuji
  • Journal Title: Clinical and Experimental Nephrology Volume: 25 Pages: 708～717
  • DOI: 10.1007/s10157-021-02048-1
  • Peer Reviewed
• [Journal Article] Antiatherosclerotic Phenotype of Perivascular Adipose Tissue Surrounding the Saphenous Vein in Coronary Artery Bypass Grafting (2021)
  • Author(s): Mikami Takuma、Furuhashi Masato、Sakai Akiko、Numaguchi Ryosuke、Harada Ryo、Naraoka Syuichi、Kamada Takeshi、Higashiura Yukimura、Tanaka Marenao、Ohori Shunsuke、Sakurada Taku、Nakamura Masanori、Iba Yutaka、Fukada Joji、Miura Tetsuji、Kawaharada Nobuyoshi
  • Journal Title: Journal of the American Heart Association Volume: 10 Pages: e018905
  • DOI: 10.1161/JAHA.120.018905
  • Peer Reviewed
• [Journal Article] Fatty liver index is independently associated with deterioration of renal function during a 10-year period in healthy subjects (2021)
  • Author(s): Takahashi Satoko、Tanaka Marenao、Furuhashi Masato、Moniwa Norihito、Koyama Masayuki、Higashiura Yukimura、Osanami Arata、Gocho Yufu、Ohnishi Hirofumi、Numata Keita、Hisasue Takashi、Hanawa Nagisa、Miura Tetsuji
  • Journal Title: Scientific Reports Volume: 11 Pages: 8606
  • DOI: 10.1038/s41598-021-88025-w
  • Peer Reviewed / Open Access
• [Journal Article] Independent association of plasma xanthine oxidoreductase activity with hypertension in nondiabetic subjects not using medication (2021)
  • Author(s): Furuhashi Masato、Higashiura Yukimura、Koyama Masayuki、Tanaka Marenao、Murase Takayo、Nakamura Takashi、Akari Seigo、Sakai Akiko、Mori Kazuma、Ohnishi Hirofumi、Saitoh Shigeyuki、Shimamoto Kazuaki、Miura Tetsuji
  • Journal Title: Hypertension Research Volume: 44 Pages: 1213～1220
  • DOI: 10.1038/s41440-021-00679-1
  • Peer Reviewed
• [Journal Article] High level of fatty liver index predicts new onset of diabetes mellitus during a 10-year period in healthy subjects (2021)
  • Author(s): Higashiura Yukimura、Furuhashi Masato、Tanaka Marenao、Takahashi Satoko、Koyama Masayuki、Ohnishi Hirofumi、Numata Keita、Hisasue Takashi、Hanawa Nagisa、Moniwa Norihito、Tsuchihashi Kazufumi、Miura Tetsuji
  • Journal Title: Scientific Reports Volume: 11 Pages: 12830
  • DOI: 10.1038/s41598-021-92292-y
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of new onset of diabetes mellitus during a 10-year period by using a combination of levels of alanine aminotransferase and γ-glutamyl transferase (2021)
  • Author(s): Miyamori Daisuke、Tanaka Marenao、Furuhashi Masato、Ohnishi Hirofumi、Koyama Masayuki、Osanami Arata、Higashiura Yukimura、Numata Keita、Hisasue Takashi、Hanawa Nagisa、Moniwa Norihito、Miura Tetsuji
  • Journal Title: Endocrine Journal Volume: 68 Pages: 1391～1402
  • DOI: 10.1507/endocrj.EJ20-0823
  • Peer Reviewed
• [Journal Article] Seasonal variation of serum 25-hydroxyvitamin D level in hemodialysis patients in the northernmost island of Japan (2021)
  • Author(s): Gocho Yufu、Tanaka Marenao、Sugawara Hirohito、Furuhashi Masato、Moniwa Norihito、Yamashita Tomohisa、Takizawa Hideki、Mukai Hiroya、Ohno Kouhei、Maeda Takuto、Osanami Arata、Ohnishi Hirofumi、Komatsu Hiroaki、Mori Kazuma、Miura Tetsuji
  • Journal Title: Clinical and Experimental Nephrology Volume: 25 Pages: 1360～1366
  • DOI: 10.1007/s10157-021-02104-w
  • Peer Reviewed
• [Journal Article] Elevated Fatty Liver Index Is Independently Associated With New Onset of Hypertension During a 10‐Year Period in Both Male and Female Subjects (2021)
  • Author(s): Higashiura Yukimura、Furuhashi Masato、Tanaka Marenao、Takahashi Satoko、Mori Kazuma、Miyamori Daisuke、Koyama Masayuki、Ohnishi Hirofumi、Moniwa Norihito、Numata Keita、Hisasue Takashi、Hanawa Nagisa、Miura Tetsuji
  • Journal Title: Journal of the American Heart Association Volume: 10 Pages: e021430
  • DOI: 10.1161/JAHA.121.021430
  • Peer Reviewed / Open Access
• [Journal Article] Distinct Regulation of U-ACE2 and P-ACE2 (Urinary and Plasma Angiotensin-Converting Enzyme 2) in a Japanese General Population (2021)
  • Author(s): Furuhashi Masato、Sakai Akiko、Tanaka Marenao、Higashiura Yukimura、Mori Kazuma、Koyama Masayuki、Ohnishi Hirofumi、Saitoh Shigeyuki、Shimamoto Kazuaki
  • Journal Title: Hypertension Volume: 78 Pages: 1138～1149
  • DOI: 10.1161/HYPERTENSIONAHA.121.17674
  • Peer Reviewed / Open Access
• [Journal Article] Independent Association of Fatty Liver Index With Left Ventricular Diastolic Dysfunction in Subjects Without Medication (2021)
  • Author(s): Furuhashi Masato、Muranaka Atsuko、Yuda Satoshi、Tanaka Marenao、Koyama Masayuki、Kawamukai-Nishida Mina、Takahashi Satoko、Higashiura Yukimura、Miyamori Daisuke、Nishikawa Ryo、Ohnishi Hirofumi、Saitoh Shigeyuki、Shimamoto Kazuaki、Miura Tetsuji
  • Journal Title: The American Journal of Cardiology Volume: 158 Pages: 139～146
  • DOI: 10.1016/j.amjcard.2021.07.047
  • Peer Reviewed
• [Journal Article] Circulating PCSK7 Level is Independently Associated with Obesity, Triglycerides Level and Fatty Liver Index in a General Population without Medication (2021)
  • Author(s): Furuhashi Masato、Kataoka Yu、Nishikawa Ryo、Koyama Masayuki、Sakai Akiko、Higashiura Yukimura、Tanaka Marenao、Saitoh Shigeyuki、Shimamoto Kazuaki、Ohnishi Hirofumi
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: Sep 25 Pages: -
  • DOI: 10.5551/jat.63159
  • Peer Reviewed / Open Access
• [Journal Article] Prediction and validation of nonalcoholic fatty liver disease by fatty liver index in a Japanese population (2021)
  • Author(s): Takahashi Satoko、Tanaka Marenao、Higashiura Yukimura、Mori Kazuma、Hanawa Nagisa、Ohnishi Hirofumi、Furuhashi Masato
  • Journal Title: Endocrine Journal Volume: Nov 19 Pages: -
  • DOI: 10.1507/endocrj.EJ21-0563
  • Peer Reviewed / Open Access
• [Journal Article] Serum uric acid level is associated with an increase in systolic blood pressure over time in female subjects: Linear mixed-effects model analyses (2021)
  • Author(s): Mori Kazuma、Furuhashi Masato、Tanaka Marenao、Higashiura Yukimura、Koyama Masayuki、Hanawa Nagisa、Ohnishi Hirofumi
  • Journal Title: Hypertension Research Volume: 45 Pages: 344～353
  • DOI: 10.1038/s41440-021-00792-1
  • Peer Reviewed
• [Presentation] CKD発症予測におけるfatty liver indexの意義 (2021)
  • Author(s): 高橋聖子, 田中希尚, 古橋眞人, 長南新太, 宮森大輔, 後町 結, 塙 なぎさ, 茂庭仁人, 大西浩文,三浦哲嗣
  • Organizer: 第64回 日本腎臓学会 学術総会
• [Presentation] CKD モデルの造影剤腎症におけるネクロプトーシスの役割 (2021)
  • Author(s): 柴田 智, 茂庭仁人, 木村 歩, 後町 結, 田中希尚, 古橋眞人, 三浦哲嗣
  • Organizer: 第64回 日本腎臓学会 学術総会
• [Presentation] 血液透析患者におけるビタミンDの季節変動に関する検討 (2021)
  • Author(s): 田中希尚, 後町 結, 菅原浩仁, 茂庭仁人, 山下智久, 古橋眞人, 滝沢英毅, 向 博也, 大野紘平, 三浦哲嗣
  • Organizer: 第66回 日本透析医学会 学術集会
• [Presentation] Fatty Liver Index (FLI) は新規高血圧発症の独立した予測因子である (2021)
  • Author(s): 東浦幸村, 古橋眞人, 田中希尚, 高橋聖子, 山下智久, 小山雅之, 大西浩文, 斎藤重幸, 塙 なぎさ,三浦哲嗣
  • Organizer: 第43回 日本高血圧学会 学術集会
• [Presentation] 一般住民におけるFatty Liver Index (FLI)と高血圧発症との関連 (2021)
  • Author(s): 東浦幸村, 古橋眞人, 田中希尚,大西浩文,三浦哲嗣
  • Organizer: 第53回 日本動脈硬化学会 学術集会
• [Presentation] 抗リン脂質抗体症候群の腎機能障害への関与が示唆されたループス腎炎の１例 (2021)
  • Author(s): 赤澤史子, 田中希尚, 山下智久, 寺沢 誠, 長南新太, 高橋聖子, 小松弘明, 安部功記, 矢野俊之, 古橋眞人, 土橋和文, 小川弥生
  • Organizer: 第51回 日本腎臓学会 東部学術大会
• [Presentation] 腎機能の自然経過し得たproliferative glomerulonephritis with monoclonal IgG depositsの一例 (2021)
  • Author(s): 田中希尚, 山下智久, 松本倫明, 遠藤圭祐, 大野絋平, 伊藤孝仁, 堀田寛之, 加藤伸郎, 三木隆幸,大岩 均, 辻 隆裕
  • Organizer: 第51回 日本腎臓学会 東部学術大会
• [Presentation] 急性腎障害が合併したBeer potomaniaによる低Na血症に持続的血液透析を施行した一例 (2021)
  • Author(s): 長南新太, 片山和規, 赤澤史子, 安部功記, 高橋聖子, 森 和真, 田中希尚, 千原伸也, 巽 博臣, 山下智久
  • Organizer: 第51回 日本腎臓学会 東部学術大会
• [Remarks] 札幌医科大学 循環器・腎臓・代謝内分泌内科学講座
  • URL: https://web.sapmed.ac.jp/im2/
• [Patent(Industrial Property Rights)] 情報処理装置、推定方法、および、推定プログラム (U-pH) (2021)
  • Inventor(s): 古橋眞人, 田中希尚, 東浦幸村, 西崎慎一郎
  • Industrial Property Rights Holder: 古橋眞人, 田中希尚, 東浦幸村, 西崎慎一郎
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2021-080028