Elucidation of pathological role of NGAL as a modulator of kidney function, metabolism and immune system

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390225
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: MORI KIYOSHI 京都大学, 医学(系)研究科(研究院), 准教授 (60343232)
• Co-Investigator(Kenkyū-buntansha): YANAGITA Motoko 京都大学, 大学院・医学研究科, 教授 (70378769) ; KAWABATA Hiroshi 京都大学, 大学院・医学研究科, 助教 (10329401)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 腎臓学 / 臓器連関 / 代謝 / 鉄 / 炎症 / 感染

Research Abstract

NGAL KO mice exhibited worsening of adenine nephropathy. 80% of blood NGAL was derived from leukocytes, while urinary NGAL was mainly synthesized by the kidney. In chronic kidney disease, urinary NGAL was partly bound to polyIg receptor or a2-macroglobulin, and showed correlation with severity of renal pathologic changes. Under high fat diet, NGAL KO mice showed resistance against obesity. Hemodialysis patients having low blood NGAL levels showed increased risk to have malnutrition and to develop severe infection. Treatment of WT mice with LPS induced brain inflammation, reduced motor activity and recognition impairment, and these chnges were ameliorated in KO mice. NGAL expression was increased in BAL fluid and lung biopsy samples from patients with idiopathic pulmonary fibrosis.

Research Products

• [Journal Article] Neutrophil gelatinase-associated lipocalin in idiopathic pulmonary fibrosis (2014)
  • Author(s): Ikezoe K, Handa T, Mori K, Watanabe K, Tanizawa K, Aihara K, Tsuruyama T, Miyagawa-Hayashino A, Sokai A, Kubo T, Muro S, Nagai S, Hirai T, Chin K, Mishima M
  • Journal Title: EurRespirJ Volume: 43 Pages: 1807-1809
  • DOI: 10.1183/09031936.00192613
• [Journal Article] Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases (2014)
  • Author(s): Kuwabara T, Mori K, Kasahara M, Yokoi H, Imamaki H, Ishii A, Koga K, Sugawara A, Yasuno S, Ueshima K, Morikawa T, Konishi Y, Imanishi M, Nishiyama A, Nakao K, Mukoyama M
  • Journal Title: PloS One Volume: 9 Pages: e88942
  • DOI: 10.1371/journal.pone.0088942
• [Journal Article] Adrenomedullin-RAMP2 System Suppresses ER Stress-Induced Tubule Cell Death and Is Involved in Kidney Protection (2014)
  • Author(s): Uetake R, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Iesato Y, Yoshizawa T, Koyama T, Yang L, Toriyama Y, Yamauchi A, Igarashi K, Tanaka M, Kuwabara T, Mori K, Yanagita M, Mukoyama M, Shindo T
  • Journal Title: PloS One Volume: 9 Pages: e87667
  • DOI: 10.1371/journal.pone.0087667
• [Journal Article] 腎臓病のすべて : 腎障害のバイオマーカーの進歩と展望 (2014)
  • Author(s): 森潔
  • Journal Title: 医学のあゆみ Volume: 249 Pages: 997-1002
• [Journal Article] Association between plasma neutrophil gelatinase associated lipocalin level and obstructive sleep apnea or nocturnal intermittent hypoxia (2013)
  • Author(s): Murase K, Mori K, Yoshimura C, Aihara K, Chihara Y, Azuma M, Harada Y, Toyama Y, Tanizawa K, Handa T, Hitomi T, Oga T, Mishima M, Chin K
  • Journal Title: PLoS One Volume: 8 Pages: e54184
  • DOI: 10.1371/journal.pone.0054184
• [Journal Article] Secreted protein lipocalin-2 promotes microglial M1 polarization (2013)
  • Author(s): Jang E, Lee S, Kim JH, Kim JH, Seo JW, Lee WH, Mori K, Nakao K, Suk K
  • Journal Title: FASEB J Volume: 27 Pages: 1176-1190
  • DOI: 10.1096/fj.12-222257
• [Journal Article] Nakao K Peritoneal fibrosis and high transport are induced in mildly pre-injured peritoneum by 3, 4-dideoxyglucosone-3-ene in mice (2013)
  • Author(s): Yokoi H, Kasahara M, Mori K, Kuwabara T, Toda N, Yamada R, Namoto S, Yamamoto T, Seki N, Souma N, Yamaguchi T, Sugawara A, Mukoyama M
  • Journal Title: Perit Dial Int Volume: 33 Pages: 143-154
  • DOI: 10.3747/pdi.2011.00033
• [Journal Article] Research Group of Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. Japan Diabetic Nephropathy Cohort Study : study design, methods, and implementation (2013)
  • Author(s): Furuichi K1, Shimizu M, Toyama T, Koya D, Koshino Y, Abe H, Mori K, Satoh H, Imanishi M, Iwano M, Yamauchi H, Kusano E, Fujimoto S, Suzuki Y, Okuda S, Kitagawa K, Iwata Y, Kaneko S, Nishi S, Yokoyama H, Ueda Y, Haneda M, Makino H, Wada T
  • Journal Title: Clin Exp Nephrol Volume: 17 Pages: 819-826
  • DOI: 10.1007/s10157-013-0778-8
• [Journal Article] Neutrophil gelatinase-associated lipocalin による病態解析 (2013)
  • Author(s): 森潔, 桒原孝成, 横井秀基, 笠原正登, 向山政志, 中尾一和
  • Journal Title: 臨床検査 Volume: 57 Pages: 617-622
• [Journal Article] Ngalの病態生理的意義 (2013)
  • Author(s): 森潔, 桒原孝成, 横井秀基, 笠原正登, 向山政志, 中尾一和
  • Journal Title: Annual Revi ew 腎臓2013 Pages: 146-149
• [Journal Article] NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease (2012)
  • Author(s): Nickolas TL, Forster CS, Sise ME, Barasch N, Valle DS, Viltard M, Buchen C, Kupferman S, Carnevali ML, Bennett M, Mattei S, Bovino A, Argentiero L, Magnano A, Devarajan P, Mori K, Erdjument-Bromage H, Tempst P, Allegri L, Barasch J
  • Journal Title: Kidney Int Volume: 82 Pages: 718-722
  • DOI: 10.1038/ki.2012.195
• [Journal Article] Regulation by lipocalin-2 of neuronal cell death, migration, and morphology (2012)
  • Author(s): S Lee, WH Lee, K Mori, and K Suk
  • Journal Title: J Neurosci Res Volume: 90 Pages: 540-550
  • DOI: 10.1002/jnr.22779
• [Journal Article] Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by toll-like receptor 4 in mice (2012)
  • Author(s): T Kuwabara, K Mori, M Mukoyama, M Kasahara, H Yokoi, Y Saito, Y Ogawa, H Imamaki, T Kawanishi, A Ishii, K Koga, KP Mori, Y Kato, A Sugawara, and K Nakao
  • Journal Title: Diabetologia Volume: 55 Pages: 2256-2266
  • DOI: 10.1007/s00125-012-2578-1
• [Journal Article] Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from aldosterone-induced glomerular injury in mice (2012)
  • Author(s): Y Ogawa, M Mukoyama, H Yokoi, M Kasahara, K Mori, Y Kato, T Kuwabara, H Imamaki, T Kawanishi, K Koga, A Ishii, T Tokudome, I Kishimoto, A Sugawara, K Nakao
  • Journal Title: J Am Soc Nephrol Volume: 23 Pages: 1198-1209
  • DOI: 10.1681/ASN.2011100985
• [Journal Article] Pleiotrophin triggers inflammation and increased peritoneal permeability leading to peritoneal fibrosis (2012)
  • Author(s): H Yokoi, M Kasahara, K Mori, Y Ogawa, T Kuwabara, H Imamaki, T Kawanishi, K Koga, A Ishii, Y Kato, KP Mori, N Toda, S Ohno, H Muramatsu, T Muramatsu, A Sugawara, M Mukoyama, and K Nakao
  • Journal Title: Kidney Int Volume: 81 Pages: 160-169
  • DOI: 10.1038/ki.2011.305
• [Journal Article] AKIの発症予測 (2012)
  • Author(s): 森潔, 中尾一和
  • Journal Title: AKI(急性腎障害)のすべて-基礎から臨床までの最新知見 Pages: 22-27
• [Journal Article] 最新の疾患バイオマーカー研究-より適切な診療を目指して- : 慢性腎臓病(CKD) (2012)
  • Author(s): 森潔, 向山政志, 笠原正登, 横井秀基, 中尾一和
  • Journal Title: 日本臨牀 Volume: 70 Pages: 864-868
• [Journal Article] 急性腎障害のバイオマーカー (2011)
  • Author(s): 森潔, 中尾一和
  • Journal Title: 腎疾患・透析最新の治療2011-2013 Pages: 295-298
• [Journal Article] 新規バイオマーカーから見た尿細管間質性腎障害 (2011)
  • Author(s): 森潔, 向山政志, 笠原正登, 中尾一和
  • Journal Title: 日本腎臓学会誌 Volume: 53 Pages: 596-599
• [Journal Article] An AKI biomarker lipocalin 2 in the blood derives from the kidney in renal injury but from neutrophils in normal and infected conditions
  • Author(s): Kanda J, Mori K, Kawabata H, Kuwabara T, Mori KP, Imamaki H, Kasahara M, Yokoi H, Mizumoto C, Thoennissen NH, Koeffler HP, Barasch J, Takaori-Kondo A, Mukoyama M, Nakao K
  • Journal Title: Clin Exp Nephrol Volume: (in press)
• [Journal Article] Macrophage-mediated glucolipotoxicity via myeloid-related protein 8/toll-like receptor 4 signaling in diabetic nephropathy
  • Author(s): Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Nakao K
  • Journal Title: Clin Exp Nephrol Volume: (in press)
• [Journal Article] Do statins play a role in renoprotection?
  • Author(s): Kasahara M, Nakagawa T, Yokoi H, Kuwabara T, Yasuno S, Mori K, Mukoyama M, Ueshima K
  • Journal Title: Clin Exp Nephrol Volume: (in press)
• [Presentation] 分泌シグナルNgalの糖脂質代謝における意義 (2014)
  • Author(s): 石井輝, 今牧博貴, 桒原孝成, 笠原正登, 横井秀基, 古賀健一, 森慶太, 加藤有希子, 戸田尚宏, 大野祥子, 菅原照, 柳田素子, 中尾一和, 向山政志, 森潔
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20140522-24
• [Presentation] 糖尿病性腎症の成因における糖・脂肪毒性の分子メカニズム (2013)
  • Author(s): 森潔, 桒原孝成, 横井秀基, 笠原正登, 向山政志
  • Organizer: 第43回日本腎臓学会西部学術大会
  • Place of Presentation: 松山
  • Year and Date: 20131110-12
  • Invited
• [Presentation] Systemic deletion of CTGF ameliorates anti-glomerular basement membrane nephritis with reduction of macrophage infiltration (2013)
  • Author(s): N Toda, K Mori (4th), et al
  • Organizer: The 46th Annual Meeting and Scientific Exposition of the American Society of Nephrology
  • Place of Presentation: Atlanta, GA
  • Year and Date: 20131107-10
• [Presentation] Megalin-independent reabsorption of low molecular weight proteins at collecting ducts revealed by drug-inducible megalin knockout mice (2013)
  • Author(s): KP Mori, K Mori (2nd), et al
  • Organizer: World Congress of Nephrology
  • Place of Presentation: Hong Kong, China
  • Year and Date: 20130531-0604
• [Presentation] Macrophage-mediated glucolipotoxicity contributes to progression of diabetic nephropathy through MRP8/TLR4 signaling (2012)
  • Author(s): T Kuwabara, K Mori (2nd), et al
  • Organizer: The 45th Annual Meeting and Scientific Exposition of the American Society of Nephrology
  • Place of Presentation: San Diego, CA
  • Year and Date: 20121101-04
• [Presentation] Analyses of microRNAs targeting CTGF in peritoneal fibrosis mouse model (2012)
  • Author(s): K Koga, K Mori (4th), et al
  • Organizer: The 45th Annual Meeting and Scientific Exposition of the American Society of Nephrology
  • Year and Date: 20121101-04
• [Presentation] 肥満におけるNgalの脂肪蓄積作用 (2012)
  • Author(s): 石井輝, 森潔, 桒原孝成, 川西智子, 今牧博貴, 笠原正登, 横井秀基, 古賀健一, 森慶太, 加藤有希子, 戸田尚宏, 大野祥子, 菅原照, 向山政志, 中尾一和
  • Organizer: 第33回日本肥満学会
  • Place of Presentation: 京都
  • Year and Date: 20121011-12
• [Presentation] 尿中Ngalと尿蛋白による慢性腎臓病患者の短期的腎予後予測 (2012)
  • Author(s): 川西智子, 森潔, 向山政志, 笠原正登, 横井秀基, 桒原孝成, 田中佐智子, 上嶋健治, 菅原照, 中尾一和
  • Organizer: 第109回日本内科学会講演会
  • Place of Presentation: 京都
  • Year and Date: 20120413-15
• [Presentation] microRNA-26a is upregulated in glomeruli of diabetic mice and attenuates TGF・1-induced extracellular matrix expression in podocytes by inhibiting both CTGF and SMAD2 (2012)
  • Author(s): K Koga, K Mori (4th), et al
  • Organizer: The 45th Annual Meeting and Scientific Exposition of the American Society of Nephrology
  • Year and Date: 20120000
• [Presentation] Inducible CTGF (CCN2) knockout mice attenuates anti-glomerular basement membrane nephritis (2012)
  • Author(s): N Toda, K Mori (4th)
  • Organizer: The 45th Annual Meeting and Scientific Exposition of the American Society of Nephrology
  • Year and Date: 20120000
• [Presentation] Alteration of renal lipid deposition and gene expression induced by fasting and high-fat diet feeding (2012)
  • Author(s): KP Mori, K Mori (2nd), et al
  • Organizer: The 45th Annual Meeting and Scientific Exposition of the American Society of Nephrology
  • Year and Date: 20120000
• [Presentation] p38 MAP kinase mediates aldosterone-induced podocyte injury in natriuretic peptide receptor (GC-A)-deficient mice (2012)
  • Author(s): Y Kato, K Mori (5th), et al
  • Organizer: The 45th Annual Meeting and Scientific Exposition of the American Society of Nephrology
  • Year and Date: 20120000
• [Presentation] Urinary level of Ngal is superior to urinary protein in prediction of chronic kidney disease progression (2011)
  • Author(s): T Kawanishi, K Mori (2nd), et al
  • Organizer: Annual Meeting of American Society of Nephrplogy
  • Place of Presentation: Philadelphia, PA
  • Year and Date: 20111110-13
• [Presentation] Analysis of acute kidney injury and its prediction by urinary biomarkers in adult Japanese ICU patients (2011)
  • Author(s): H Ujike, K Mori (4th), et al
  • Organizer: Annual Meeting of American Society of Nephrplogy
  • Year and Date: 20111110-13
• [Presentation] 尿中バイオマーカーの新知見 (2011)
  • Author(s): 森潔, 向山政志, 笠原正登, 横井秀基, 中尾一和
  • Organizer: 第41回日本腎臓学会西部学術大会
  • Place of Presentation: 徳島
  • Year and Date: 20110930-1001
  • Invited
• [Presentation] Lessons from analysis of a single urinary biomarker, Ngal (2011)
  • Author(s): K Mori, M Mukoyama, J Barasch and K Nakao
  • Organizer: The 9th Japan Human Proteome Conference
  • Place of Presentation: Niigata, Japan
  • Year and Date: 20110728-30
  • Invited
• [Presentation] AKIと CKDのバイオマーカー (2011)
  • Author(s): 森潔, 向山政志, 笠原正登, 横井秀基, 桒原孝成, 中尾一和
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20110615-17
  • Invited
• [Presentation] The kidney and neutrophils are the major sources of acute kidney injury biomarker NGAL (2011)
  • Author(s): K Mori, J Kanda, M Mukoyama, H Kawabata, M Kasahara, H Yokoi, T Kuwabara and K Nakao
  • Organizer: World Congress of Nephrology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20110408-12
• [Presentation] Incomplete tubular compensation model for albuminuria in diabetes (2011)
  • Author(s): K Mori, M Mukoyama, M Kasahara, H Yokoi, T Kuwabara, H Imamaki, T Kawanishi, A Ishii, K Koga, KP Mori, Y Kato, A Sugawara and K Nakao
  • Organizer: World Congress of Nephrology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20110408-12
• [Presentation] Hyperlipidemia promotes diabetic renal injury via TLR4 signaling (2011)
  • Author(s): T Kuwabara, K Mori (2nd author), et al
  • Organizer: World Congress of Nephrology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20110408-12
• [Presentation] Pleiotrophin causes peritoneal inflammation and mesothelial cell proliferation in a mouse model of peritoneal fibrosis (2011)
  • Author(s): H Yokoi, K Mori (4th), et al
  • Organizer: World Congress of Nephrology
  • Year and Date: 20110408-12
• [Presentation] Aggravation of diabetic nephropathy by hyperlipidemia is mediated by MRP8/TLR4 signaling in macrophages (2011)
  • Author(s): T Kuwabara, K Mori (2nd), et al
  • Organizer: Annual Meeting of American Society of Nephrplogy
  • Year and Date: 20110000
• [Presentation] Blockade of p38 MAPK pathway ameliorates aldosterone-induced renal injury in guanylyl cyclase-A deficient mice (2011)
  • Author(s): Y Kato, K Mori (5th), et al
  • Organizer: Annual Meeting of American Society of Nephrplogy
  • Year and Date: 20110000
• [Presentation] Acute disruption of megalin expression in renal cortex reveals compensatory reabsorption capacity of low molecular weight proteins in S3 segment of proximal tubules and collecting ducts
  • Author(s): KP Mori, K Mori (2nd), et al
  • Organizer: The 45th Annual Meeting and Scientific Exposition of the American Society of Nephrology
• [Book] 心腎連関と内分泌代謝.最新内分泌代謝学 (2013)
  • Author(s): 森潔
  • Total Pages: 341-342
  • Publisher: 診断と治療社
• [Book] 糸球体の構造・機能と糸球体過剰濾過. 病態から学ぶ新腎臓内科学 (2011)
  • Author(s): 森潔
  • Total Pages: 6-8
  • Publisher: 診断と治療社
• [Book] 急性腎不全・急性腎障害. 病態から学ぶ新腎臓内科学 (2011)
  • Author(s): 森潔
  • Total Pages: 62-66
  • Publisher: 診断と治療社
• [Remarks] 京都大学大学院医学研究科メディカルイノベーションセンター・TMKプロジェクト
  • URL: http://www.tmk.med.kyoto-u.ac.jp/mori.html
• [Remarks] 京都大学教育研究活動データベース
  • URL: http://www.tmk.med.kyoto-u.ac.jp/mori.html