Clarification of suppressive effects of ONO-1301 on the progression of chronic kidney disease and its mechanisms

• Project/Area Number: 22790791
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Okayama University
• Principal Investigator: NASU Tatsuyo 岡山大学, 医学部, 客員研究員 (70572741)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 慢性腎臓病 / 腎線維化 / 糖尿病性腎症 / プロスタサイクリン / 線維化 / 炎症 / HGF / EMT / 炎症細胞 / TGF-β1 / 尿細管上皮細胞

Research Abstract

The number of patients with chronic kidney disease(CKD) requiring dialysis therapy is increasing. ONO-1301 is a long-acting prostacyclin(PGI2) agonist and possesses thromboxane A2 synthase inhibitory effects. In the present study, therapeutic effects of ONO-1301 on tubulointerstitial injuries and diabetic nephropathy mediated via anti-fibrotic, anti-inflammatory and via inducing HGF, were observed, suggesting the potential of ONO-1301 in suppressing the progression of CKD.

Research Products

• [Journal Article] A sustained-release prostacyclin analog ONO-1301 ameliorates tubulointerstitial alterations in a mouse obstructive nephropathy model (2012)
  • Author(s): Nasu T, Kinomura M, Tanabe K, Yamasaki H, Htay SL, Saito D, Hinamoto N, Watatani H, Ujike H, Suzuki Y, Sugaya T, Sugiyama H, Sakai Y, Matsumoto K, Maeshima Y, Makino H
  • Journal Title: Am J Physiol-Renal Physiol Volume: 302巻(in press)
  • Peer Reviewed
• [Journal Article] A sustained-release prostacyclin analog ONO-1301 ameliorates tubulointerstitial alterations in a mouse obstructive nephropathy model (2012)
  • Author(s): Nasu T
  • Journal Title: Am J Physiol-Renal Physiol
  • Peer Reviewed
• [Journal Article] Amelioration of renal alterations in obese type 2 diabetic mice by Vasohibin-1, a negative feedback regulator of angiogenesis (2011)
  • Author(s): Saito D, Maeshima Y, Nasu T, Yamasaki H, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H
  • Journal Title: Am J Physiol-Renal Physiol Volume: 300巻 Pages: 873-886
  • Peer Reviewed
• [Journal Article] Intermittent administration of a sustained-release prostacyclin analog ONO-1301 ameliorates renal alterations in a rat type 1 diabetesmodel (2011)
  • Author(s): Yamasaki H, Maeshima Y, Nasu T, Saito D, Tanabe K, Hirokoshi-Kawahara K, Sugiyama H, Sakai Y, Makino H
  • Journal Title: Prostag Leukotr Ess Volume: 84巻 Pages: 99-107
  • Peer Reviewed
• [Journal Article] Intermittent administration of a sustained-release prostacyclin analog ONO-1301 ameliorates renal alterations in a rat type 1 diabetes model (2011)
  • Author(s): Yamasaki H
  • Journal Title: Prostag Leukotr Ess Volume: 84 Pages: 99-107
  • Peer Reviewed
• [Journal Article] Amelioration of renal alterations in obese type 2 diabetic mice by Vasohibin-1, a negative feedback regulator of angiogenesis (2011)
  • Author(s): Saito D
  • Journal Title: Am J Physiol-Renal Physiol Volume: 300
  • Peer Reviewed
• [Journal Article] Peramivir for severe influenza infection in a patient with diabetic nephropathy (2010)
  • Author(s): Nasu T
  • Journal Title: Am J Respir Crit Care Med Volume: 182 Pages: 1209-1210
  • Peer Reviewed
• [Presentation] ONO-1301, a sustained-release prostacyclin analog, ameliorates renal alterations in a mouse type 2 diabetes model through its direct protective effects on mesangial cells (2011)
  • Author(s): Yamasaki H
  • Organizer: 米国腎臓学会
  • Place of Presentation: Philadelphia
  • Year and Date: 2011-11-11
• [Presentation] 内因性血管新生抑制因子Vasohibin-1の片側尿管結紮モデルにおける腎間質線維化抑制効果の検討 (2011)
  • Author(s): 綿谷博雪
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-06-17
• [Presentation] ONO-1301による2型糖尿病性腎症進展抑制効果の基礎的検討 (2011)
  • Author(s): 山崎浩子
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-06-16
• [Presentation] Intermittent administration of ONO-1301, a sustained-release prostacyclin analog, ameliorates renal alterations in obese type 2 diabetes mice (2010)
  • Author(s): Yamasaki H
  • Organizer: 米国腎臓学会
  • Place of Presentation: Denver
  • Year and Date: 2010-11-16
• [Presentation] Prostacyclin analog ONO-1301 ameliorates tubulointerstitial alterations through induction of HGF (2010)
  • Author(s): Nasu T
  • Organizer: 国腎臓学会
  • Place of Presentation: Denver
  • Year and Date: 2010-11-16
• [Presentation] 徐放性ONO-1301による2型糖尿病モデルにおける腎症治療効果の検討 (2010)
  • Author(s): 山崎浩子
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2010-06-16
• [Presentation] ONO-1301による尿細管間質病変抑制効果におけるHGFの関与についての検討 (2010)
  • Author(s): 那須達世
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2010-06-16
• [Presentation] ONO-1301MS, a sustained-release prostacyclin analog, ameliorates renal damage in obese type 2 diabetic mice (2010)
  • Author(s): Yamasaki H
  • Organizer: ISN-NEXUS Kyoto in 2010
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2010-04-15
• [Presentation] Prostacyclin analog ONO-1301 ameliorates tubulointerstitial alterations via induction of HGF in a mouse UUO model (2010)
  • Author(s): Nasu T
  • Organizer: ISN-NEXUS Kyoto in 2010
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2010-04-15
• [Presentation] Protective effects of anti-angiogenic Vasohibin-1 on podocytes in obese type 2 diabetic mice (2010)
  • Author(s): Saito D
  • Organizer: ISN-NEXUS Kyoto in 2010
  • Place of Presentation: 京都国際会館
• [Presentation] ONO-1301 MS, a sustained-release prostacyclin analog, ameliorates renal damage in obese type 2 diabetic mice (2010)
  • Author(s): Yamasaki H
  • Organizer: ISN-NEXUS Kyoto in 2010
  • Place of Presentation: 京都国際会館
• [Presentation] Prostacyclin analog ONO-1301 ameliorates tubulointerstitial alterations via induction of HGF in a mouse UUO model (2010)
  • Author(s): Nasu T
  • Organizer: ISN-NEXUS Kyoto in 2010
  • Place of Presentation: 京都国際会館
• [Presentation] Renal expression of Vasohibin-1, a novel endothelium-derived angiogenesis inhibitor, in patients with renal disorders (2010)
  • Author(s): Hinamoto N
  • Organizer: 2010年度米国腎臓学会議
  • Place of Presentation: デンバー、米国
• [Presentation] Plasma and urinary levels of Vasohibin-1 in patients with chronic kidney disease (2010)
  • Author(s): Saito D
  • Organizer: 2010年度米国腎臓学会議
  • Place of Presentation: デンバー、米国
• [Presentation] Intermittent administration of ONO-1301, a sustained-release prostacyclin analog, ameliorates renal alterations in obese type 2 diabetes mice (2010)
  • Author(s): Yamasaki H
  • Organizer: 2010年度米国腎臓学会議
  • Place of Presentation: デンバー、米国
• [Presentation] Prostacyclin analog ONO-1301 ameliorates tubulointerstitial alterations through induction of HGF (2010)
  • Author(s): Nasu T
  • Organizer: 2010年度米国腎臓学会議
  • Place of Presentation: デンバー、米国
• [Presentation] 徐放性ONO-1301による2型糖尿病モデルにおける腎症治療効果の検討 (2010)
  • Author(s): 山崎浩子
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場
• [Presentation] ONO-1301による尿細管間質病変抑制効果におけるHGFの関与についての検討 (2010)
  • Author(s): 那須達世
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 慢性腎臓病患者における血管新生制御因子Vasohibin-1濃度変化とその臨床的意義 (2010)
  • Author(s): 斎藤大輔
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 糖尿病性腎症における血管新生制御因子Vasohibin-1による糸球体足細胞保護効果の基礎的検討 (2010)
  • Author(s): 斎藤大輔
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場