Application to the clarification and treatment of molecular mechanism of iron metabolic disorders in hypertension

• Project/Area Number: 25750044
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Kyushu University
• Principal Investigator: Tajima Soichiro 九州大学, 大学病院, その他 (10579460)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 鉄代謝 / 高血圧症 / angiotensin II / ヘプシジン / 酸化ストレス / アンジオテンシンII / マクロファージ / iron regulatory protein / 鉄代謝関連蛋白質 / 鉄 / hepcidin

Outline of Final Research Achievements

We examined the effect of Ang II on duodenal iron transporters, hepatic hepcidin, and body iron storage. Serum hepcidin-25 concentration was lower in Ang II-infused mice compared to vehicle-treated mice, and this decrease was ameliorated by angiotensin II type 1 receptor antagonist administration. Protein expression of FPN and DMT1 was increased in the duodenum of Ang II-treated mice. Iron content was elevated in kidney and peritoneal macrophage from Ang II-treated mice. These results suggest that Ang II involves in body iron metabolism through the regulation of duodenal iron transporters via hepatic hepcidin and the alteration of body iron distribution. Inhibition of Ang II has a beneficial effect on correction of abnormal iron metabolism induced by Ang II.

Research Products

• [Journal Article] Pemetrexed-Induced Rash May Be Prevented by Supplementary Corticosteroids (2015)
  • Author(s): Takumi Sakurada, Soji Kakiuchi, Soichiro Tajima, Yuya Horinouchi, Ken Konaka, Naoto Okada, Hirotaka Nishisako, Toshimi Nakamura, Kazuhiko Teraoka, Kazuyoshi Kawazoe, Hiroaki Yanagawa, Yasuhiko Nishioka, Keisuke Ishizawa
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 11 Pages: 1752-1756
  • DOI: 10.1248/bpb.b15-00435
  • NAID: 130005106388
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics and risk factors of interstitial lung disease induced by chemotherapy for lung cancer (2015)
  • Author(s): Takumi Sakurada, Soji Kakiuchi, Soichiro Tajima, Yuya Horinouchi, Naoto Okada, Hirotaka Nishisako, Toshimi Nakamura, Kazuhiko Teraoka, Kazuyoshi Kawazoe, Hiroaki Yanagawa, Yasuhiko Nishioka, Kazuo Minakuchi, Keisuke Ishizawa
  • Journal Title: The Annals Pharmacotherapy Volume: 49(4) Issue: 4 Pages: 398-404
  • DOI: 10.1177/1060028014566446
  • Peer Reviewed / Open Access
• [Journal Article] Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice (2015)
  • Author(s): Soichiro Tajima, Yasumasa Ikeda, Hideaki Enomoto, Imao Mizuki, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Rihito Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki
  • Journal Title: European Journal of Nutrition Volume: 印刷中 Issue: 5 Pages: 709-719
  • DOI: 10.1007/s00394-014-0749-1
  • NAID: 120006732013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction. (2014)
  • Author(s): Ikeda Y, Ozono I, Tajima S, Imao M, Horinouchi Y, Izawa-Ishizawa Y, Kihira Y, Miyamoto L, Ishizawa K, Tsuchiya K, Tamaki T.
  • Journal Title: PLoS One. Volume: 9 Issue: 2 Pages: e89355-e89355
  • DOI: 10.1371/journal.pone.0089355
  • Peer Reviewed / Open Access
• [Journal Article] Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice (2013)
  • Author(s): Yasumasa Ikeda, Hideaki Enomoto, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya, Toshiaki Tamaki
  • Journal Title: Am J Physiol Renal Physiol. Volume: 304(7)
  • Peer Reviewed
• [Journal Article] Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia. (2013)
  • Author(s): Ikeda Yasumasa, et al
  • Journal Title: J Cardiovasc Pharmacol Volume: 未定 Issue: 5 Pages: 423-429
  • DOI: 10.1097/fjc.0b013e318287d526
  • Peer Reviewed
• [Presentation] 呼吸器がん領域におけるイリノテカン塩酸塩投与患者の治療安全に対するUGT1A1遺伝子多型の影響 (2014)
  • Author(s): 田島 壮一郎
  • Organizer: 第31回日本薬学会九州支部大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-12-06 – 2014-12-07
  • Invited
• [Presentation] 肺癌薬物療法における薬剤性間質性肺炎の発症とそのリスク因子の解析 (2014)
  • Author(s): 櫻田 巧, 柿内 聡司, 田島 壮一郎, 寺岡 和彦, 中村 敏己, 川添 和義, 西岡 安彦, 楊河 宏章, 水口 和生
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] アンジオテンシンIIは鉄吸収制御と生体内鉄分布変化に関与する (2014)
  • Author(s): 池田 康将, 田島 壮一郎, 堀ノ内 裕也, 石澤 有紀, 木平 孝高, 宮本 理人, 石澤 啓介, 土屋 浩一郎, 玉置 俊晃
  • Organizer: 第125回日本薬理学会近畿部会
  • Place of Presentation: 岡山
  • Year and Date: 2014-06-20
• [Presentation] Iron metabolic disorders in hypertension (2014)
  • Author(s): Soichiro Tajima, Nobuaki Egashira, Satohiro Masuda
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台国際センター
• [Presentation] アンジオテンシンIIは十二指腸鉄輸送体発現とマクロファージ鉄量を増加させる (2014)
  • Author(s): 池田 康将, 田島 壮一郎, 石澤 有紀, 木平 孝高, 石澤 啓介, 土屋 浩一郎, 玉置 俊晃
  • Organizer: 第43回日本心脈管作動物質学会
  • Place of Presentation: 神戸国際会議場