遺伝子・環境因子からの尿路結石症予防の研究-メタボリックシンドロームとの関連-

2011 年度 研究成果報告書

• 研究課題/領域番号: 21592076
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 泌尿器科学
• 研究機関: 名古屋市立大学
• 研究代表者: 藤田 圭治 名古屋市立大学, 大学院・医学研究科, 研究員 (50264734)
• 研究分担者: 伊藤 恭典 名古屋市立大学, 大学院・医学研究科, 研究員 (70295608) ; 安井 孝周 名古屋市立大学, 大学院・医学研究科, 講師 (40326153) ; 戸澤 啓一 名古屋市立大学, 大学院・医学研究科, 准教授 (40264733) ; 郡 健二郎 名古屋市立大学, 大学院・医学研究科, 教授 (30122047)
• 研究期間 (年度): 2009 – 2011
• キーワード: 尿路結石症 / メタボリックシンドローム / アディポサイトカイン / ストレス感受性シグナル / オステオポンチン / 結石モデルマウス / OPNノックアウトマウス / OPNトランスジェニックマウス

研究概要

私たちの最近の研究から、尿路結石症はメタボリックシンドロームの発症機序と似ていることがわかってきた。そこで、本研究ではその観点からみた尿路結石症予防法の確立をめざし、遺伝因子と環境因子の両面から基礎研究を行った。遺伝因子の研究として、OPN遺伝子のSNPs解析を行い、その結果と患者の背景・結石成分を比較し、再発リスクマーカーとなり得るSNPsを見つけ出した。環境因子の研究として、ストレス感受性シグナルであるNFκB,が増加し、ミトコンドリアが酸化ストレスにより傷害を受けたことを確認した。

研究成果

• [雑誌論文] The role of long-term loading of cholesterol in renal crystal formation (2011)
  • 著者名/発表者名: Itoh Yasunori, Yoshimura Mugi, Niimi Kazuhiro, Usami Masayuki, Hamamoto Shuzo, Kobayashi Takahiro, Hirose Masahito, Okada Atsushi, Yasui Takahiro, Tozawa Keiichi, Kohri Kenjiro
  • 雑誌名: Archivio Italiano di Urologia e Andrologia 巻: 83 ページ: 23-5
  • 査読あり
• [雑誌論文] Efficacy of selective α1A adrenoceptor antagonist silodosin in the medical expulsive therapy for ureteral stones (2011)
  • 著者名/発表者名: Itoh Yasunori, Okada Atsushi, Yasui Takahiro, Hamamoto Shuzo, Hirose Masahito, Kojima Yoshiyuki, Tozawa Keiichi, Sasaki Shoichi, Kohri Kenjiro
  • 雑誌名: International Journal of Urology 巻: 18 ページ: 672-674
  • 査読あり
• [雑誌論文] The Mechanism of renal stone formation and renal failure induced by administration of melamine and cyanuric acid (2010)
  • 著者名/発表者名: Kobayashi Takahiro, Okada Atsushi, Fujii Yasuhiro, Niimi Kazuhiro, Hamamoto Shuzo, Yasui Takahiro, Tozawa Keiichi, Kohri Kenjiro
  • 雑誌名: Urological Research 巻: 38 ページ: 117-125
  • 査読あり
• [雑誌論文] Renal tubular epithelial cell injury and oxidative stress induce calcium oxalate crystal formation in mouse kidney (2010)
  • 著者名/発表者名: Hirose Masahito, Yasui Takahiro, Okada Atsushi, Hamamoto Shuzo, Shimizu Hideo, Itoh Yasunori, Tozawa Keiichi, Kohri Kenjiro
  • 雑誌名: International Journal of Urology 巻: 17 ページ: 83-93
  • 査読あり
• [雑誌論文] The single-knot method with Lapra-Ty clips is useful for training surgeons in vesicourethral anastomosis during laparoscopic radical prostatectomy (2009)
  • 著者名/発表者名: Yasui Takahiro, Itoh Yasunori, Maruyama Tetsuji, Akita Hidetoshi, Hashimoto Yoshihiro, Tozawa Keiichi, Kohri Kenjiro
  • 雑誌名: International Urology and Nephrology 巻: 41 ページ: 281-285
  • 査読あり
• [雑誌論文] Genome-wide analysis of genes related to kidney stone formation and elimination in the calcium oxalate nephrolithiasis model mouse : detection of stone-preventive factors and involvement of macrophage activity (2009)
  • 著者名/発表者名: Okada Atsushi, Yasui Takahiro, Hamamoto Shuzo, Hirose Masahito, Kubota Yasue, Itoh Yasunori, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro
  • 雑誌名: Journal of Bone and Mineral Research 巻: 24 ページ: 908-24
  • 査読あり
• [雑誌論文] Alendronate reduces the excretion of risk factors for calcium phosphate stone formation in postmenopausal women with osteoporosis (2009)
  • 著者名/発表者名: Yasui Takahiro, Itoh Yasunori, Okada Atsushi, Hamamoto Shuzo, Hirose Masahito, Kobayashi Takahiro, Tozawa Keiichi, Kohri Kenjiro
  • 雑誌名: Urologia Internationalis 巻: 83 ページ: 226-229
  • 査読あり
• [雑誌論文] Effects of silodosin and naftopidil on distal ureter and cardiovascular system in anesthetized dogs : Comparison of potential medications for distal ureteral stone passage (2009)
  • 著者名/発表者名: Kobayashi Shinya, Tomiyama Yoshitaka, Hoyano Yuji, Yamazaki Yoshinobu, Sasaki Shoichi, Kohri Kenjiro
  • 雑誌名: Journal of Urology 巻: 183 ページ: 357-361
  • 査読あり
• [雑誌論文] Gene expressions and mechanical functions of α1-adrenoceptro subtypes in mouse ureter (2009)
  • 著者名/発表者名: Kobayashi Shinya, Tomiyama Yoshitaka, Hoyano Yuji, Yamazaki Yoshinobu, Kusama Hiroshi, Itoh Yasunori, Kubota Yasue, Kohri Kenjiro
  • 雑誌名: World Journal of Urology 巻: 27 ページ: 775-780
  • 査読あり
• [雑誌論文] Evaluation of operative complications related to laparoscopic radical prostatectomy (2008)
  • 著者名/発表者名: Tozawa Keiichi, Hashimoto Yoshihiro, Yasui Takahiro, Itoh Yasunori, Nagata Daisuke, Akita Hidetoshi, Kawai Noriyasu, Hayashi Yutaro, Kohri Kenjiro
  • 雑誌名: International Journal of Urology 巻: 15 ページ: 222-225
  • 査読あり
• [雑誌論文] Prevalence and epidemiological characteristics of urolithiasis in Japan : National trends between 1965 and 2005 (2008)
  • 著者名/発表者名: Yasui Takahiro, Iguchi Masanori, Suzuki Sadao, Kohri Kenjiro
  • 雑誌名: Urology 巻: 71 ページ: 209-213
  • 査読あり
• [雑誌論文] Impact of microwave tissue coagulation during laparoscopic partial nephrectomy on postoperative renal function (2008)
  • 著者名/発表者名: Yasui Takahiro, Itoh Yasunori, Kojima Yoshiyuki, Umemoto Yukihiro, Tozawa Keiichi, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • 雑誌名: International Urology and Nephrology 巻: 40 ページ: 277-282
  • 査読あり
• [雑誌論文] Eicosapentaenoic acid has a preventive effect on the recurrence of nephrolithiasis (2008)
  • 著者名/発表者名: Yasui Takahiro, Suzuki Sadao, Itoh Yasunori, Tozawa Keiichi, Tokudome Shinkan, Kohri Kenjiro
  • 雑誌名: Urologia Internationali 巻: 81 ページ: 135-138
  • 査読あり
• [雑誌論文] NF-κB activation in renal tubular epithelial cells by oxalate stimulation (2008)
  • 著者名/発表者名: Tozawa Keiichi, Yasui Takahiro, Okada Atsushi, Hirose Masahito, Hamamoto Shuzo, Itoh Yasunori, Kohri Kenjiro
  • 雑誌名: International Journal of Urology 巻: 15 ページ: 924-928
  • 査読あり
• [雑誌論文] Risk of renal stone formation induced by long-term bed rest could be decreased by premedication with bisphosphonate and increased by resistive exercise (2008)
  • 著者名/発表者名: Okada Atsushi, Ohshima Hiroshi, Itoh Yasunori, Yasui Takahiro, Tozawa Keiichi, Kohri Kenjiro
  • 雑誌名: International Journal of Urology 巻: 15 ページ: 630-635
  • 査読あり
• [雑誌論文] Prevalence and epidemiologic characteristics of lower urinary tract stones in Japan (2008)
  • 著者名/発表者名: Yasui Takahiro, Iguchi Masanori, Suzuki Sadao, Okada Atsushi, Itoh Yasunori, Tozawa Keiichi, Kohri Kenjiro
  • 雑誌名: Urology 巻: 72 ページ: 1001-1005
  • 査読あり
• [学会発表] Efficacy of a selective alpha 1A adrenoceptor antagonist as a medical exclusive therapy against ureteral stones (2011)
  • 著者名/発表者名: Itoh Yasunori, Okada Atsushi, Yasui Takahiro, Taguchi Kazumi, Niimi Kazuhiro, Fujii Yasuhiro, Hirose Yasuhiko, Usami Masayuki, Hamamoto Shuzo, Hirose Masahito, Fujita Keiji, Tozawa Keiichi, Kohri Kenjiro
  • 学会等名: 1^<st> Meeting ofthe EAUSection of Urolithiasis(EULIS)
  • 発表場所: London(United Kingdom)
  • 年月日: 20110907-10
• [学会発表] Overexpression of Cdc25A, an androgen receptor coactivator, in human prostage cancer (2009)
  • 著者名/発表者名: Hashimoto Yoshihiro, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Satisfaction with voiding, appearance, and sexual function in adolescents after hypospadias repair during childhood (2009)
  • 著者名/発表者名: Nakane Akihiro, Hayashi Yutaro, Kurokawa Satoshi, Kamisawa Hideyuki, Imura Makoto, Mizuno Kentaro, Kato Toshiki, Kojima Yoshiyuki, Maruyama Tetsuji, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Disturbance of testicular development during testicular tubule formation causes vanishing testis (2009)
  • 著者名/発表者名: Hayashi Yutaro, Kojima Yoshiyuki, Mizuno Kentaro, Kurokawa Satoshi, Nakane Akihiro, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Relationship between testicular location and the genetic characteristics of germ cells in cryptorchidism (2009)
  • 著者名/発表者名: Mizuno Kentaro, Kojima Yoshiyuki, Kurokawa Satoshi, Iwatsuki Shoichiro, Kamisawa Hideyuki, Shibata Yasuhiro, Maruyama Tetsuji, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Expression of the estrogen receptor alpha is decreased in the cryptorchid rat testes (2009)
  • 著者名/発表者名: Mizuno Kentaro, Kojima Yoshiyuki, Kurokawa Satoshi, Iwatsuki Shoichiro, Kamisawa Hideyuki, Shibata Yasuhiro, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] The new findings of signal intensity on T2-weighted-MR imaging may enable preoperative diagnosis of vanishing testes (2009)
  • 著者名/発表者名: Kato Toshiki, Kojima Yoshiyuki, Mizuno Kentaro, Kamisawa Hideyuki, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Prostate growth inhibition by subtype-selective alpha1-adrenoceptor antagonist naftopidil in benign prostatic hyperplasia (2009)
  • 著者名/発表者名: Kojima Yoshiyuki, Sasaki Shoichi, Oda Nobuyuki, Hayase Masa, Kubota Yasue, Hayashi Yutaro, Kiniwa Mamoru, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Alendronate has a preventive effect on the recurrence of nephrolithiasis by reducing the risk factors of calcium stone (2009)
  • 著者名/発表者名: Yasui Takahiro, Okada Atsushi, Usami Masayuki, Hamamoto Shuzo, Kobayashi Takahiro, Hirose Masahito, Itoh Yasunori, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Dietary soy isoflavone replacement improves detrusor overactivity of ovariectomized rats with alteration of connexin-43 expression in the urinary bladder (2009)
  • 著者名/発表者名: Okada Shinsuke, Kojima Yoshiyuki, Hamamoto Shuzo, Mizuno Kentaro, Kubota Yasue, Sasaki Shoichi, Tsugaya Masayuki, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Genome-wide association study identifies new susceptibility loci for urolithiasis (2009)
  • 著者名/発表者名: Usami Masayuki, Itoh Yasunori, Tozawa Keiichi, Matsuda Koichi, Nakamura Yusuke, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Osteopontin has an important role in kidney stone formation and elimination via renal macrophage recruitment and activation (2009)
  • 著者名/発表者名: Okada Atsushi, Tozawa Keiichi, Niimi Kazuhiro, Hirose Yasuhiko, Kobayashi Takahiro, Usami Masayuki, Hamamoto Shuzo, Hirose Masahito, Itoh Yasunori, Yasui Takahiro, Hayashi Yutaro, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Cyclooxygenase-2 appears to be induced in the testes of experimental cryptorchidism in order to reduce the apoptosis of germ cells and may have a key role on protection of germ cells from heat-stress (2009)
  • 著者名/発表者名: Kubota Hiroki, Kubota Yasue, Umemoto Yukihiro, Kaneko Tomoyoshi, Yanai Yoshimasa, Sasaki Shoichi, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Essential role of Chk1 in S phase progression through regulation of RNR2 expression (2009)
  • 著者名/発表者名: Naruyama Hiromichi, Hashimoto Yoshiyuki, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] Effects of microgravity enhancement of oxidative stress in human renal tubular cells (2009)
  • 著者名/発表者名: Itoh Yasunori, Yasui Takahiro, Okada Atsushi, Hirose Masahito, Hamamoto Shuzo, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] The melamine stone : The mechanism of renal calculus formation from melamine exposure (2009)
  • 著者名/発表者名: Kobayashi Takahiro, Okada Atsushi, Usami Masayuki, Hamamoto Shuzo, Hirose Masahito, Yasui Takahiro, Itoh Yasunori, Tozawa Keiichi, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30
• [学会発表] The role of NF-KB on renal stone formation (2009)
  • 著者名/発表者名: Tozawa Keiichi, Yasui Takahiro, Hirose Masahito, Usami Masayuki, Hamamoto Shuzo, Hirose Yasuhiko, Okada Atsushi, Itoh Yasunori, Hayashi Yutaro, Kohri Kenjiro
  • 学会等名: AUA 2009 Annual Meeting
  • 発表場所: Chicago(USA)
  • 年月日: 20090425-30