Analysis on the renoprotective effects and clinical significance of endogenous Vasohibin family in chronic kidney disease

• Project/Area Number: 23591193
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Okayama University
• Principal Investigator: MAESHIMA YOHEI 岡山大学, 医歯(薬)学総合研究科, 教授 (10343287)
• Co-Investigator(Renkei-kenkyūsha): SATO Yasufumi 東北大学, 加齢医学研究所腫瘍循環分野, 教授 (50178779)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 慢性腎臓病 / 血管新生 / 糖尿病性腎症 / Vasohibin-1 / 尿細管間質障害 / 線維化 / 血管内皮細胞 / 炎症

Research Abstract

The population of CKD patients in Japan is estimated as 13.3 million people. CKD is a risk factor of end-stage renal disease and cardiovascular disorders. Here, we examined the functional role of Vasohibin-1, a negative feedback regulator of angiogenesis, in CKD. Diabetic nephropathy, tubulointerstitial injuries induced by unilateral ureteral obstruction and acute kidney injury were exacerbated in the Vasofibin-1+/-- mice compared with the wild-type mice. Renal Vasohibin-1 expression was associated with crescentic lesions and interstitial inflammation in CKD patients. Elevated plasma/urinary levels of Vasohibin-1 predicted progressive renal functional deterioration in CKD patients. These results suggest the potential renoprotective effects of Vasohibin-1 and its potential as a novel biomarker in CKD.

Research Products

• [Journal Article] Renal distribution of Vasohibin-1 in patients with chronic kidney disease (2014)
  • Author(s): Hinamoto N, Maeshima Y, Saito D, Yamasaki H, Tanabe K, Nasu T, Watatani H, Ujike H, Kinomura M, Sugiyama H, Sonoda H, Kanomata N, Sato Y, Makino H
  • Journal Title: Acta Medica Okayama Volume: in press
  • NAID: 120005465585
  • Peer Reviewed
• [Journal Article] Upstream stimulatory factors 1 and 2 mediate the transcription of angiotensin II binding and inhibitory protein. (2013)
  • Author(s): Matsuda M, Tamura K, Wakui H, Maeda A, Ohsawa M, Kanaoka T, Azushima K, Uneda K, Haku S, Tsurumi-Ikeya Y, Toya Y, Maeshima Y, Yamashita A, Umemura S.
  • Journal Title: J Biol Chem. Volume: 288(26) Issue: 26 Pages: 19238-49
  • DOI: 10.1074/jbc.m113.451054
  • Peer Reviewed / Open Access
• [Journal Article] A decreased level of serum soluble Klotho is an independent biomarker associated with arterialstiffness in patients with chronic kidney disease (2013)
  • Author(s): Kitagawa M, Sugiyama H, Morinaga H, Inoue T, Takiue K, Ogawa A, Yamanari T, Kikumoto Y, Uchida HA, Kitamura S, Maeshima Y, Nakamura K, Ito H, Makino H.
  • Journal Title: PLoS ONE Volume: 8 Issue: 2 Pages: e56695-e56695
  • DOI: 10.1371/journal.pone.0056695
  • Peer Reviewed
• [Journal Article] Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy (2012)
  • Author(s): Tanabe K, Tamura Y, Lanaspa MA, Miyazaki M, Suzuki N, Sato W, Maeshima Y, Schreiner GF, Villarreal FJ, Johnson RJ, Nakagawa T
  • Journal Title: Am J Physiol-Renal Physiol Volume: 303巻 Issue: 9 Pages: F1264-F1274
  • DOI: 10.1152/ajprenal.00227.2012
  • 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, 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 Issue: 12 Pages: F1616-F1629
  • DOI: 10.1152/ajprenal.00538.2011
  • Peer Reviewed
• [Journal Article] Effluent free radicals are associated with residual renal function and predict technique failure in peritoneal dialysis patients (2012)
  • Author(s): Morinaga H, Sugiyama H, Inoue T, Maeshima Y, Makino H, et al.
  • Journal Title: Perit Dial Int Volume: 32 Pages: 453-461
  • 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, Kinomura M, Tanabe K, Matsumoto K, Maeshima Y, Makino H, at al.
  • Journal Title: Am J Physiol-Renal Physiol Volume: 302
  • Peer Reviewed
• [Journal Article] Suppression of adiponectin by aberrantly glycosylated IgA1 in glomerular mesangial cells in vitro and in vivo (2012)
  • Author(s): Inoue T, Sugiyama H, Kitagawa M, Maeshima Y, Makino H, et al.
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy (2012)
  • Author(s): Tanabe K, Tamura Y, Lanaspa MA, Maeshima Y, Johnson RJ, Nakagawa T, et al.
  • Journal Title: Am J Physiol-Renal Physiol Volume: 303
  • 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 Issue: 4 Pages: F873-F886
  • DOI: 10.1152/ajprenal.00503.2010
  • 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, Maeshima Y, Nasu T, Saito D, Tanabe K, Hirokoshi-Kawahara K, Sugiyama H, Sakai Y, Makino H
  • Journal Title: Prostag Leukotr Ess Volume: 84 Pages: 99-107
  • Peer Reviewed
• [Journal Article] Involvement of Runx3 in the basal transcriptional activation of the mouse angiotensin II type 1 receptor-associated protein gene (2011)
  • Author(s): Matsuda M, Tamura K, Wakui H, Dejima T, Maeda A, Ohsawa M, Kanaoka T, Haku S, Azushima K, Yamasaki H, Saito D, Hirose T, Maeshima Y, Nagashima Y, Umemura S
  • Journal Title: Physiol Genomics Volume: 43 Pages: 884-894
  • Peer Reviewed
• [Journal Article] Abnormalities of glycogenes in tonsillar lymphocytes in IgA nephropathy (2011)
  • Author(s): Inoue T, Sugiyama H, Kitagawa M, Takiue K, Morinaga H, Kikumoto Y, Maeshima Y, Fukushima K, Nishizaki K, Akagi H, Hiki Y, Makino H
  • Journal Title: Adv Otorhinolaryngol Volume: 72 Pages: 71-74
  • Peer Reviewed
• [Journal Article] High glucose increases metallothionein expression in renal proximal tubular epithelial cells (2011)
  • Author(s): Ogawa D, Asanuma M, Miyazaki I, Tachibana H, Wada J, Sogawa N, Sugaya T, Kitamura S, Maeshima Y, Shikata K, Makino H
  • Journal Title: Exp Diabetes Res Volume: 2011 Pages: 534872-534872
  • Peer Reviewed
• [Journal Article] Serum high sensitivity troponin T is a significant biomarker of left ventricular diastolic dysfunction in subjects with non-diabetic chronic kidney disease (2011)
  • Author(s): Kitagawa M, Sugiyama H, Morinaga H, Inoue T, Takiue K, Kikumoto Y, Uchida HA, Kitamura S, Maeshima Y, Toh N, Nakamura K, Itoh H, Makino H
  • Journal Title: Nephron Extra Volume: 1 Pages: 166-177
  • Peer Reviewed
• [Journal Article] 慢性腎臓病患者の心血管イべントリスク管理におけるストロングスタチンの可能性 -自験例の提示を含めて (2011)
  • Author(s): 前島洋平, 斎藤大輔, 槇野博史
  • Journal Title: Therapeutic Research Volume: 32 Pages: 811-820
  • Peer Reviewed
• [Journal Article] CKDとその治療管理の歴史とガイドライン (2011)
  • Author(s): 綿谷博雪, 前島洋平,槇野博史
  • Journal Title: Medical Practice Volume: 28 Pages: 972-977
• [Journal Article] Renal distribution of Vasohibin-1 in patients with chronic kidney disease
  • Author(s): Hinamoto N, Maeshima Y, Saito D, Yamasaki H, Tanabe K, Nasu T, Watatani H, Ujike H, Kinomura M, Sugiyama H, Sonoda H, Kanomata N, Sato Y, Makino H
  • Journal Title: Acta Medica Okayama Volume: (In press)
  • NAID: 120005465585
  • Peer Reviewed
• [Presentation] Protective Effects of Endogenous Vasohibin-1 on Podocyte in Diabetic Nephropathy (2013)
  • Author(s): Hinamoto N (Maeshima Y)
  • Organizer: 2013年度米国腎臓学会議
  • Place of Presentation: アトランタ、米国
  • Year and Date: 2013-11-07
• [Presentation] Analysis on the mechanisms involved in aggravation of renal alterations in diabetic Vasohibin-1 knockout mice (2013)
  • Author(s): Maeshima Y, Hinamoto N, Yamasaki H, Watatani H, Ujike H, Tanabe K, Sugiyama H, Sato Y, Makino H
  • Organizer: World Congress of Nephrology 2013
  • Place of Presentation: Hong Kong, China
• [Presentation] Unique environmental risk factors of CKD: Life-style related disorders as risk factors for Chronic Kidney Disease in a community-based population in Japan (2013)
  • Author(s): Maeshima Y, Makino H
  • Organizer: The 7th Asian Forum of CKD Initiative
  • Place of Presentation: Pattaya, Thailand
  • Invited
• [Presentation] Protective Effects of Endogenous Vasohibin-1 on Podocyte in Diabetic Nephropathy (2013)
  • Author(s): Hinamoto N, Maeshima Y, Yamasaki H, Watatani H, Ujike H, Tanabe K, Masuda K, Sugiyama H, Sato Y, Makino H
  • Organizer: American Society of Nephrology 2013
  • Place of Presentation: Atlanta, USA
• [Presentation] Novel Prostacyclin Analog ONO-1301 (SR-ONO) Ameliorates AKI in a Rat Experimental Contrast-Induced Nephropathy Model (2013)
  • Author(s): Ujike H, Maeshima Y, Hinamoto N, Watatani H, Masuda K, Tanabe K, Sugiyama H, Sakai Y, Makino H
  • Organizer: American Society of Nephrology 2013
  • Place of Presentation: Atlanta, USA
• [Presentation] Therapeutic Effects of ONO-1301 on Vascular Calcification in a Rat Model of Adenine-Induced Chronic Kidney Disease (2013)
  • Author(s): Maeshima Y, Watatani H, Hinamoto N, Tanabe K, Masuda K, Ujike H, Sugiyama H, Sakai Y, Makino H
  • Organizer: American Society of Nephrology 2013
  • Place of Presentation: Atlanta, USA
• [Presentation] Lack of Vasohibin-1 exacerbates tubulo- interstitial injuries partly via activating Smad3 and excessive matrix production in renal fibroblasts (2012)
  • Author(s): Watatani H (Maeshima Y)
  • Organizer: 2012年度米国腎臓学会議
  • Place of Presentation: サンディエゴ,米国
  • Year and Date: 2012-11-01
• [Presentation] Lack of Vasohibin-1 Exacerbates Renal Alterations Induced by Infusion of Angiotensin-II (2012)
  • Author(s): Hiroko Yamasaki, Yohei Maeshima, Hiroyuki Watatani, Masaru Kinomura, Norikazu Hinamoto, Haruyo Ujike, Hitoshi Sugiyama, Yasufumi Sato, Hirofumi Makino
  • Organizer: ASN Kidney Week 2012
  • Place of Presentation: San Diego convention Center, San Diego, California, USA
• [Presentation] Lack of Vasohibin-1 Exacerbates Tubulointerstitial Injuries Partly via Activating Smad3 and Excessive Matrix Production in Renal Fibroblasts (2012)
  • Author(s): Hiroyuki Watatani, Yohei Maeshima, Hiroko Yamasaki, Norikazu Hinamoto, Haruyo Ujike, Hitoshi Sugiyama, Yasufumi Sato, Hirofumi Makino
  • Organizer: ASN Kidney Week 2012
  • Place of Presentation: San Diego convention Center, San Diego, California, USA
• [Presentation] Aggravation of inflammatory and fibrotic alterations of diabetic nephropathy in mice lacking Vasohibin-1 (2012)
  • Author(s): Norikazu Hinamoto, Yohei Maeshima, Daisuke Saito, Hiroko Yamasaki, Tatsuyo Nasu, Hiroyuki Watatani, Masaru Kinomura, Haruyo Ujike, Hitoshi Sugiyama, Yasufumi Sato and Hirofumi Makino
  • Organizer: ASN Kidney Week 2012
  • Place of Presentation: San Diego convention Center, San Diego, California, USA
• [Presentation] Elevated plasma levels of Vasohibin-1 predict renal dysfunction and renal levels of Vasohibinb-1 are associated with histological alterations in CKD patients (2012)
  • Author(s): Norikazu Hinamoto, Yohei Maeshima, Yasufumi Sato, Hirofumi Makino, et al.
  • Organizer: ASN Kidney Week 2012
  • Place of Presentation: San Diego convention Center, San Diego, California, USA
• [Presentation] Urinary levels of prostanoid metabolites predict for acute kidney injury in adult Japanese heterogenous ICU patients (2012)
  • Author(s): Haruyo Ujike, Yohei Maeshima, Masaru Kinomura, Hirofumi Makino, et al.
  • Organizer: ASN Kidney Week 2012
  • Place of Presentation: San Diego convention Center, San Diego, California, USA
• [Presentation] 糖尿病性腎症の進展における炎症の関与と新規治療アプローチ (2011)
  • Author(s): 前島洋平, 斎藤大輔, 山崎浩子, 酒井芳紀, 佐藤靖史, 槇野博史
  • Organizer: 第54回日本腎臓学会学術総会(招待講演)
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] 腎疾患における血管新生制御因子Vasohibin-1の発現変化と機能解析 (2011)
  • Author(s): 前島洋平, 雛元紀和, 綿谷博雪, 杉山 斉, 佐藤靖史, 槇野博史
  • Organizer: 第54回日本腎臓学会学術総会(招待講演)
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] 腎疾患患者における血管新生制御因子Vasohibin-1の発現変化とその臨床的意義についての検討 (2011)
  • Author(s): 雛元紀和, 前島洋平, 斎藤大輔, 山崎浩子, 綿谷博雪, 杉山 斉, 鹿股直樹, 園田 光, 佐藤靖史, 槇野博史
  • 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）
• [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, 前島洋平, 山崎浩子, 斎藤大輔, 木野村賢, 那須達世, 雛元紀和, 杉山 斉, 佐藤靖史, 園田 光, 槇野博史
  • 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）
• [Presentation] 内因性血管新生抑制因子Vasohibin-1の1型糖尿病モデルにおける腎症進展 抑制効果の検討 (2011)
  • Author(s): 雛元紀和, 前島洋平, 斎藤大輔, 山崎浩子, 綿谷博雪, 杉山 斉, 園田 光, 佐藤靖史, 槇野博史
  • 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）
• [Presentation] 糖尿病性腎症における血管新生制御因子Vasohibin-1によるnephrin発現回復効果の基礎的検討 (2011)
  • Author(s): 斎藤大輔, 前島洋平, 雛元紀和, 綿谷博雪, 山崎浩子, 木野村賢, 喜多村真治, 杉山 斉, 園田 光, 佐藤靖史, 槇野博史
  • 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）
• [Presentation] Accelerated tubulointerstitial alterations induced by unilateral ureteral obstruction in mice lacking Vasohibin-1 (2011)
  • Author(s): Watatani H, Maeshima Y, Saito D, Yamasaki H, Kinomura M, Hinamoto N, Mizuhara K, Sugiyama H, Sonoda H, Sato Y, Makino H
  • Organizer: World Congress of Nephrology (WCN) 2011
  • Place of Presentation: Vancouver Convention Center, Vancouver, Canada
• [Presentation] Renal expression of Vasohibin-1, a novel endothelium-derived angiogenesis inhibitor, in patients with renal disorders (2011)
  • Author(s): Hinamoto N, Maeshima Y, Saito D, Yamasaki H, Watatani H, Kinomura M, Kitamura S, Sugiyama H, Kanomata N, Sonoda H, Sato Y, Makino H
  • Organizer: World Congress of Nephrology (WCN) 2011
  • Place of Presentation: Vancouver Convention Center, Vancouver, Canada
• [Presentation] Exacerbated diabetic renal alterations in mice lacking Vasohibin-1 (2011)
  • Author(s): Hinamoto N, Maeshima Y, Saito D, Yamasaki H, Watatani H, Ujike H, Sugiyama H, Sonoda H, Sato Y, Makino H
  • Organizer: ASN Kidney Week 2011
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia, PA, USA
• [Presentation] Immunohistochemical analysis of Vasohibin-1 using renal biopsy specimens of patients with renal disorders (2011)
  • Author(s): Hinamoto N, Maeshima Y, Saito D, Yamasaki H, Watatani H, Ujike H, Kitamura S, Sugiyama H, Kanomata N, Sonoda H, Sato Y, Makino H
  • Organizer: ASN Kidney Week 2011
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia, PA, USA
• [Presentation] Accelerated tubulointerstitial alterations induced by unilateral ureteral obstruction in mice lacking Vasohibin-1 (2011)
  • Author(s): Watatani H, Maeshima Y, Saito D, Yamasaki H, Kinomura M, Hinamoto N, Ujike H, Sugiyama H, Sonoda H, Sato Y, Makino H
  • Organizer: ASN Kidney Week 2011
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia, PA, USA
• [Book] CKDフォトブック (2013)
  • Author(s): 槇野博史、前島洋平
  • Total Pages: 51
  • Publisher: シスメックス株式会社
• [Book] 腎疾患・透析最新の治療2011-2013 (2011)
  • Author(s): 前島洋平, 槇野博史
  • Total Pages: 454
  • Publisher: 南江堂
• [Patent(Industrial Property Rights)] バゾヒビン含有治療剤 (2013)
  • Inventor(s): 前島洋平、那須達世、田邊克幸、 佐藤靖史、槇野博史
  • Industrial Property Rights Holder: 国立大学法人 岡山大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-04-26
  • Overseas
• [Patent(Industrial Property Rights)] 糖尿病性腎症の治療用医薬組成物 (2012)
  • Inventor(s): 前島洋平,一瀬邦弘,槇野博史
  • Industrial Property Rights Holder: 国立大学法人 岡山大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-07-27
  • Overseas