To clarify the mechanism of chronic kidney disease progression by uremic toxins and its application for the treatment

• Project/Area Number: 20590974
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Shimane University
• Principal Investigator: YANO Shozo Shimane University, 医学部, 講師 (80403450)
• Co-Investigator(Renkei-kenkyūsha): SUGIMOTO Toshitsugu 島根大学, 医学部, 教授 (00226458)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 尿毒素 / 終末糖化産物 / 血管平滑筋細胞 / 血管石灰化 / 血管内皮細胞 / 副甲状腺ホルモン

Research Abstract

In vascular endothelial cells, one of uremic toxins, phenyl acetic acid stimulates reactive oxygen species (ROS) production and TNFα in a dose-dependent manner, and ROS inhibitor TEMPOL suppressed TNFα secretion. In vascular smooth muscle cells (VSMC), advanced glycation end-products (AGEs) stimulate NADPH oxidase activity followed by ROS generation, which may play important roles in an osteoblastic trans-differentiation from VSMC and vascular calcification.

Research Products

• [Journal Article] Phenylacetic acid stimulates reactive oxygen species generation and tumor necrosis factor-a secretion in vascular ndothelial cells. (2011)
  • Author(s): Morita M, Yano S, Yamaguchi T, Yamauchi M, Sugimoto T
  • Journal Title: Ther Apheresis Dial. 15(2) Pages: 147-150
  • Peer Reviewed
• [Journal Article] The calcium-sensing receptor and calcimimetics in blood pressure modulation. (2011)
  • Author(s): Smajilovic S, Yano S, Jabbari R, Tfelt-Hansen J
  • Journal Title: Br J Pharmacol. in press
  • Peer Reviewed
• [Journal Article] Asymmetric dimethylarginine as a risk factor for cardiovascular disease in Japanese patients with type 2 diabetes ellitus. (2011)
  • Author(s): Kanazawa I, Yano S, Notsu Y, Yamaguchi T, Nabika T, Sugimoto T
  • Journal Title: Clin Endocrinol (Oxf). 74(4) Pages: 467-72
  • Peer Reviewed
• [Journal Article] 腎移植レシピエントの骨脆弱性を誘発する要因 (2011)
  • Author(s): 矢野彰三
  • Journal Title: 腎と骨代謝 Vol.24(1) Pages: 15-22
• [Journal Article] Phenylacetic acid stimulates reactive oxygen species generation and tumor necrosis factor-a secretion in vascular endothelial cells. (2011)
  • Author(s): Morita M, Yano S, Yamaguchi T, et al
  • Journal Title: Ther Apheresis Dial. Volume: 15 Pages: 147-150
  • Peer Reviewed
• [Journal Article] The calcium-sensing receptor and calcimimetics in blood pressure modulation. (2011)
  • Author(s): Smajilovic S, Yano S, Jabbari R, et al
  • Journal Title: Br J Pharmacol. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Asymmetric dimethylarginine as a risk factor for cardiovascular disease in Japanese patients with type 2 diabetes mellitus. (2011)
  • Author(s): Kanazawa I, Yano S, Yamaguchi T, et al
  • Journal Title: Clin Endocrinol (Oxf). Volume: 74 Pages: 467-472
  • Peer Reviewed
• [Journal Article] Relationships between dimethylarginine and the presence of vertebral fractures in type 2 diabetes mellitus. (2010)
  • Author(s): Kanazawa I, Yano S, Yamaguchi T, Notsu Y, Nabika T, Sugimoto T
  • Journal Title: Clin Endocrinol (Oxf). 73(4) Pages: 463-8
  • Peer Reviewed
• [Journal Article] Calcium-corrected Intact PTH : A Clinically Useful Parameter for Quantifying Parathyroid Function in Patients Undergoing Hemodialysis. (2010)
  • Author(s): Yano S, Brown EM, Takase H, Wada A, Suzuki K, Kobayashi A, Sugimoto T
  • Journal Title: Nephron Clin Pract. 115 Pages: 51-58
  • Peer Reviewed
• [Journal Article] Bone metabolism after cinacalcet administration in patients with secondary hyperparathyroidism. (2010)
  • Author(s): Yano S, Suzuki K, Sumi M, Tokumoto A, Shigeno K, Himeno Y, Sugimoto T
  • Journal Title: J Bone Miner Metab. 28 Pages: 49-54
  • NAID: 10027206582
  • Peer Reviewed
• [Journal Article] 続発性骨粗鬆症における骨折リスク (2010)
  • Author(s): 矢野彰三, 杉本利嗣
  • Journal Title: CLINICAL CALCIUM Vol.19(9) Pages: 771-776
• [Journal Article] 慢性腎臓病と骨折 (2010)
  • Author(s): 矢野彰三
  • Journal Title: The BONE Vol.24(4) Pages: 347-352
• [Journal Article] Calcium-corrected Intact PTH : A Clinically Useful Parameter for Quantifying Parathyroid Function in Patients Undergoing Hemodialysis. (2010)
  • Author(s): Yano S, Brown EM, Takase H, et al
  • Journal Title: Nephron Clin Pract. 115
  • Peer Reviewed
• [Journal Article] Bone metabolism after cinacalcet administration in patients with secondary hyperparathyroidism. (2010)
  • Author(s): Yano S, Suzuki K, Sumi M, et al
  • Journal Title: J Bone Miner Metab 28 Pages: 49-54
  • NAID: 10027206582
  • Peer Reviewed
• [Journal Article] Parathyroid Hormone Upregulates BMP-2 mRNA Expression Through Mevalonate Kinase and Rho Kinase Inhibition in Osteoblastic MC3T3-E1 Cells. (2009)
  • Author(s): Takase H, Yano S, Yamaguchi T, Kanazawa I, Hayashi K, Yamamoto M, Yamauchi M, Sugimoto T
  • Journal Title: Horm Metab Res. 41 Pages: 861-865
  • Peer Reviewed
• [Journal Article] 私の処方維持血液透析中の二次性副甲状腺機能亢進症に対する内科的治療 (2009)
  • Author(s): 矢野彰三, 杉本利嗣
  • Journal Title: Modern Physician 29(4) Pages: 534-535
• [Journal Article] 生体におけるリンの分布と生理的意義:存在様式,分布,生理機能 (2009)
  • Author(s): 矢野彰三, 杉本利嗣
  • Journal Title: CLINICAL CALCIUM Vol.19(6) Pages: 771-776
• [Journal Article] 脊椎圧迫骨折と食道裂孔ヘルニア,Gastro Report整形外科領域における消化管疾患 (2009)
  • Author(s): 矢野彰三
  • Journal Title: Salvus Vol.3(4)
• [Journal Article] Parathyroid Hormone Upregulates BMP-2 mRNA Expression Through Mevalonate Kinase and Rho Kinase Inhibition in Osteoblastic MC3T3-E1 Cells. (2009)
  • Author(s): Takase H, Yano S, Yamaguchi T, et al
  • Journal Title: Horm Metab Res. 41 Pages: 861-865
  • Peer Reviewed
• [Journal Article] Activation of AMP-kinase and inhibition of Rho-kinase induce the mineralization of osteoblastic MC3T3-E1 cells through endothelial NOS and BMP-2 expression. (2009)
  • Author(s): Kanazawa I, Yamaguchi T, Yano S, et al
  • Journal Title: Am J Physiol Endocrinol Metab 296
  • Peer Reviewed
• [Journal Article] BMP/Wnt antagonists are upregulated by dexamethasone in osteoblasts and reversed by alendronate and PTH : potential therapeutic targets for glucocorticoid-induced osteoporosis. (2009)
  • Author(s): Hayashi K, Yamaguchi T, Yano S, et al
  • Journal Title: Biochem Bi ophys Res Commun 379 Pages: 261-266
  • Peer Reviewed
• [Journal Article] Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. (2009)
  • Author(s): Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Kurioka S, Yano S, Sugimoto T
  • Journal Title: J Clin Endocrinol Metab 94 Pages: 45-49
  • Peer Reviewed
• [Journal Article] Relationships between serum adiponectin levels versus bone mineral density, bone metabolic markers, and vertebral fracturesin type 2 diabetes mellitus. (2009)
  • Author(s): Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T
  • Journal Title: Eur J Endocrinol 160 Pages: 265-273
  • Peer Reviewed
• [Journal Article] Association between Erythropoietin Requirements and Antihypertensive Agents. (2008)
  • Author(s): Yano S, Suzuki K, et al
  • Journal Title: Nephron Clin Pract 109
  • Peer Reviewed
• [Journal Article] Calcium receptor expression and function in oligodendrocyte commitment and lineage progression : Potential impact on reduced myelin basic protein in CaR-null mice (2008)
  • Author(s): Chattopadhyay N, Espinosa-Jeffrey A, Tfelt-Hansen J, Yano S, Bandyopadhyay S, Brown EM, de Vellis J
  • Journal Title: J Neurosci Res 86 Pages: 2159-2167
  • Peer Reviewed
• [Journal Article] Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression (2008)
  • Author(s): Kanazawa I, Yamaguchi T, Yano S, Yamauchi M, Sugimoto T
  • Journal Title: Biochem Biophys Res Commun 375 Pages: 414-419
  • Peer Reviewed
• [Journal Article] Combination of obesity with hyperglycemia is a risk factor for the presence of vertebral fractures in type 2 diabetic men. (2008)
  • Author(s): Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T
  • Journal Title: Calcif Tissue Int 83 Pages: 324-331
  • Peer Reviewed
• [Journal Article] Serum DHEA-S level is associated with the presence of atherosc lerosis in postmenopausal women with type 2 diabetes mellitus. (2008)
  • Author(s): Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Kurioka S, Yano S, Sugimoto T
  • Journal Title: Endocr J 55 Pages: 667-675
  • NAID: 10022609033
  • Peer Reviewed
• [Presentation] Assessment of bone tissue composition in patients undergoing dialysis therapy using Raman spectrometry. (2010)
  • Author(s): Yano S, Iwasaki Y, Tokumoto A, Yamato H, Yamaguchi T, Sugimoto T
  • Organizer: The 32^<th> American Society for Bone and Mineral Research
  • Place of Presentation: Toronto, Canada
• [Presentation] Weight gain is associated with a decrease in eGFR in middle-aged Japanese ; a 5-year follow-up study. (2010)
  • Author(s): Yano S, Nabika T, Sugimoto T
  • Organizer: 14^<th> International Society of Nephrology
  • Place of Presentation: Kyoto
• [Presentation] Weight gain is associated with a decrease in eGFR in middle-aged dwelling people. (2010)
  • Author(s): Yano S, Nabika T, Sugimoto T
  • Organizer: 14^<th> International Congress of Endocrinology
  • Place of Presentation: Kyoto
• [Presentation] 透析女性に対するラロキシフェンの効果～3年間の縦断検討～ (2010)
  • Author(s): 矢野彰三, 角昌晃, 名和田清子, 景山明美, 姫野安敏, 杉本利嗣
  • Organizer: 第55回日本透析医学会学術集会・総会
  • Place of Presentation: 神戸
• [Presentation] Parathyroid Hormone Upregulates BMP-2 mRNA Expression Through Mevalonate Kinase and Rho Kinase Inhibition in Osteoblastic MC3T3-E1 Cells. (2009)
  • Author(s): Takase H, Yano S, Yamaguchi T, Kanazawa I, Hayashi K, Yamamoto M, Yamauchi M, Sugimoto T
  • Organizer: The 31^<th> American Society for Bone and Mineral Research
  • Place of Presentation: Denvar, USA
• [Presentation] 当院透析患者における神経障害の実態 (2009)
  • Author(s): 藤原良江、安井ひとみ、板倉文子、石飛真寿子、門脇千春、岡田理江、山根晴香、矢野彰三、姫野安敏
  • Organizer: 第55回日本透析医学会学術集会・総会
  • Place of Presentation: 神戸
• [Presentation] 一般住民における腎機能低下に対する肥満の関与 (2009)
  • Author(s): 矢野彰三, 並河徹, 杉本利嗣
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] シナカルセトの血清Ca低下作用:骨吸収・骨形成のアンカップリングの関与 (2009)
  • Author(s): 矢野彰三, 鈴木恵子, 角昌晃, 滋野和志, 姫野安敏, 徳本明秀, 公受伸之, 杉本利嗣
  • Organizer: 第54回日本透析医学会学術集会・総会
  • Place of Presentation: 横浜
• [Presentation] 副甲状腺ホルモンは骨芽細胞においてメバロン酸-Rhoキナーゼ経路を介してBMP-2mRNA発現を亢進する (2009)
  • Author(s): 矢野彰三, 山口徹, 高瀬裕史, 金沢一平, 林公美, 山内美香, 山本昌弘, 杉本利嗣
  • Organizer: 第27回日本骨代謝学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Acute change in serum ionized calcium directly affects bone formation independent of PTH action during hemodialysis. (2008)
  • Author(s): Yano S, Yamaguchi T, Suzuki K, Sumi M, Himeno Y, Sugimoto T
  • Organizer: The 30^<th> American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada
• [Presentation] 尿毒症物質フェニル酢酸は腎不全による低回転骨の原因物質である (2008)
  • Author(s): 矢野彰三, 山口徹, 金沢一平, 小川典子, 林公美, 山内美香, 杉本利嗣
  • Organizer: 第51回日本腎臓学会学術総会
  • Place of Presentation: 福岡
• [Presentation] 透析患者における副甲状腺機能定量化の試み:島根県の現状 (2008)
  • Author(s): 高瀬裕史, 矢野彰三, 鈴木恵子, 山口徹, 杉本利嗣
  • Organizer: 第53回日本透析医学会学術集会・総会
  • Place of Presentation: 神戸
• [Presentation] Acute change in serum ionized calcium directly affects bone formation independent of PTH action during hemodialysis. (2008)
  • Author(s): S. Yano, T. Yamaguchi, K. Suzuki, et al
  • Organizer: The 30^<th> American Society for Bone and Mineral Research
  • Place of Presentation: Montreal
• [Presentation] 透析患者における副甲状腺機能定量化の試み (2008)
  • Author(s): 高瀬裕史, 矢野彰三, 鈴木恵子, 山口徹, 杉本利嗣
  • Organizer: 第53回日本透析医学会学術集会・総会
  • Place of Presentation: 神戸
• [Book] 副甲状腺腫瘍の疫学.日本臨床69増刊号2 (2011)
  • Author(s): 矢野彰三, 杉本利嗣
• [Book] 副甲状腺腫瘍の疫学 (2011)
  • Author(s): 矢野彰三, 杉本利嗣
  • Total Pages: 731
  • Publisher: 日本臨床29(3):407-410,2011
• [Book] 骨代謝とその調節機構.CKD-MBDハンドブック(編著:深川雅史) (2009)
  • Author(s): 矢野彰三
  • Publisher: 日本メディカルセンター東京
• [Book] 糖尿病と骨病変.CKD-MBDハンドブック(編著:深川雅史) (2009)
  • Author(s): 矢野彰三, 杉本利嗣
  • Publisher: 日本メディカルセンター東京
• [Book] CKD-MBDハンドブック (2009)
  • Author(s): 矢野彰三(編著:深川雅史)
  • Total Pages: 253
  • Publisher: 日本メディカルセンター
• [Remarks] ホームページ等