M Nangaku

Summary

Affiliation: University of Tokyo
Country: Japan

Publications

  1. ncbi Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    J Am Soc Nephrol 17:17-25. 2006
  2. ncbi Involvement of endoplasmic reticulum (ER) stress in podocyte injury induced by excessive protein accumulation
    Reiko Inagi
    Molecular and Cellular Nephrology, Institute of Medical Sciences, Tokai University, Kanagawa, Japan
    Kidney Int 68:2639-50. 2005
  3. ncbi A severe diabetic nephropathy model with early development of nodule-like lesions induced by megsin overexpression in RAGE/iNOS transgenic mice
    Reiko Inagi
    Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan
    Diabetes 55:356-66. 2006
  4. ncbi Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress
    Pisut Katavetin
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Biochem Biophys Res Commun 359:928-34. 2007
  5. ncbi A new model of renal microvascular injury
    M Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Japan
    Curr Opin Nephrol Hypertens 7:457-62. 1998
  6. ncbi ET(B) receptor protects the tubulointerstitium in experimental thrombotic microangiopathy
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Kidney Int 62:922-8. 2002
  7. ncbi Hypoxia and hypoxia-inducible factor in renal disease
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Nephron Exp Nephrol 110:e1-7. 2008
  8. ncbi Pathogenesis and prognosis of thrombotic microangiopathy
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Clin Exp Nephrol 11:107-14. 2007
  9. ncbi Novel drugs and the response to hypoxia: HIF stabilizers and prolyl hydroxylase
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Recent Pat Cardiovasc Drug Discov 1:129-39. 2006
  10. ncbi Hypoxia and the HIF system in kidney disease
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo, Japan
    J Mol Med (Berl) 85:1325-30. 2007

Detail Information

Publications93

  1. ncbi Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    J Am Soc Nephrol 17:17-25. 2006
    ..This has given hope for the development of novel therapeutic approaches against this final common pathway...
  2. ncbi Involvement of endoplasmic reticulum (ER) stress in podocyte injury induced by excessive protein accumulation
    Reiko Inagi
    Molecular and Cellular Nephrology, Institute of Medical Sciences, Tokai University, Kanagawa, Japan
    Kidney Int 68:2639-50. 2005
    ..CONCLUSION: This paper implicates a crucial role for the accumulation of excessive proteins in the podocyte ER in the induction of ER stress and associated podocyte injury...
  3. ncbi A severe diabetic nephropathy model with early development of nodule-like lesions induced by megsin overexpression in RAGE/iNOS transgenic mice
    Reiko Inagi
    Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan
    Diabetes 55:356-66. 2006
    ..This multiple hit approach is of interest in consideration of the sequential events during development of diabetic nephropathy...
  4. ncbi Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress
    Pisut Katavetin
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Biochem Biophys Res Commun 359:928-34. 2007
    ..This renoprotection was associated with up-regulation of HO-1 in the kidney. In conclusion, EPO-induced HO-1 expression is likely to provide cytoprotection against oxidative stress...
  5. ncbi A new model of renal microvascular injury
    M Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Japan
    Curr Opin Nephrol Hypertens 7:457-62. 1998
    ..This study briefly reviews the consequences of glomerular endothelial cell injury or activation, as shown by recent experimental data...
  6. ncbi ET(B) receptor protects the tubulointerstitium in experimental thrombotic microangiopathy
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Kidney Int 62:922-8. 2002
    ..The endothelin ET(B) receptor has been shown to mediate both endothelial cell proliferation and vasodilation, and we therefore hypothesized that blockade of this receptor might promote more severe injury in this model...
  7. ncbi Hypoxia and hypoxia-inducible factor in renal disease
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Nephron Exp Nephrol 110:e1-7. 2008
    ..Because HIF is activated only to suboptimal levels in various pathogenic states, therapeutic activation holds promise as a novel and effective approach to the future care of end-stage renal disease...
  8. ncbi Pathogenesis and prognosis of thrombotic microangiopathy
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Clin Exp Nephrol 11:107-14. 2007
    ..Etiological diagnosis at the bedside and the development of disease-specific therapeutic modalities will enable us to optimize the management of patients with TMA and improve their prognosis in the future...
  9. ncbi Novel drugs and the response to hypoxia: HIF stabilizers and prolyl hydroxylase
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Recent Pat Cardiovasc Drug Discov 1:129-39. 2006
    ..This review highlights the identification of novel HIF stabilizers as specific molecularly targeted therapies against cardiovascular disease...
  10. ncbi Hypoxia and the HIF system in kidney disease
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo, Japan
    J Mol Med (Berl) 85:1325-30. 2007
    ..Studies utilizing HIF-stimulating agents proved efficacy in various kidney disease models, suggesting that HIF activation is an ideal target of future therapeutic approaches...
  11. ncbi Pathogenesis of renal anemia
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Semin Nephrol 26:261-8. 2006
    ..As with other anemias, the consequences of renal anemia are a moderate decrease in tissue oxygen tensions and counterregulatory mechanisms that maintain total oxygen consumption, including a persistent increase in cardiac output...
  12. ncbi Hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Nephron Exp Nephrol 98:e8-12. 2004
    ..Recent studies have elucidated the mechanisms of hypoxia-induced transcription, giving hope for the development of novel therapeutic approaches against this final common pathway...
  13. ncbi Role of chronic hypoxia and hypoxia inducible factor in kidney disease
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo 113-8655, Japan
    Chin Med J (Engl) 121:257-64. 2008
  14. ncbi Cloning of rodent megsin revealed its up-regulation in mesangioproliferative nephritis
    M Nangaku
    Molecular and Cellular Nephrology, Institute of Medical Sciences Tokai University School of Medicine, Kanagawa, Japan
    Kidney Int 60:641-52. 2001
    ..Megsin is a novel member of the serine protease inhibitor (serpin) superfamily. To elucidate functional roles of this gene, we cloned megsin in rodents and investigated its role in a rat nephritis model...
  15. ncbi Angiotensin-induced hypoxia in the kidney: functional and structural changes of the renal circulation
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Adv Exp Med Biol 618:85-99. 2007
    ..This has given hope for the development of novel therapeutic approaches against hypoxia in the kidney...
  16. ncbi Mechanisms of immune-deposit formation and the mediation of immune renal injury
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Bunkyo ku, Tokyo, 113 8655, Japan
    Clin Exp Nephrol 9:183-91. 2005
    ..Particularly promising future therapeutic approaches include selective immunosuppression and interference in complement activation and C5b-9-mediated cell injury...
  17. ncbi Complement regulatory proteins in glomerular diseases
    M Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Kidney Int 54:1419-28. 1998
    ..Systemic administration of soluble recombinant complement regulatory proteins and local overexpression of complement regulatory proteins are promising therapeutic approaches...
  18. ncbi Blockade of calcium influx through L-type calcium channels attenuates mitochondrial injury and apoptosis in hypoxic renal tubular cells
    Tetsuhiro Tanaka
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1, Hongo, Bunkyo ku, Tokyo, Japan
    J Am Soc Nephrol 15:2320-33. 2004
    ....
  19. ncbi Specific tissue distribution of megsin, a novel serpin, in the glomerulus and its up-regulation in IgA nephropathy
    R Inagi
    Molecular and Cellular Nephrology, Tokai University School of Medicine, Kanagawa, Japan
    Biochem Biophys Res Commun 286:1098-106. 2001
    ....
  20. ncbi Protective role of nitric oxide in a model of thrombotic microangiopathy in rats
    J Shao
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    J Am Soc Nephrol 12:2088-97. 2001
    ..The absence of effects with L-NIL treatment suggests a minor role for inducible NOS in this model. These results suggest that production of NO, most likely by endothelial cells, is an important protective mechanism in TMA...
  21. ncbi Expression of megsin mRNA, a novel mesangium-predominant gene, in the renal tissues of various glomerular diseases
    D Suzuki
    Division of Nephrology and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan
    J Am Soc Nephrol 10:2606-13. 1999
    ..These data suggest a link of megsin expression to the pathogenesis of IgA-N and DN, two major causes of end-stage renal failure...
  22. ncbi Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury
    K Yamada
    Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan
    Kidney Int 59:137-46. 2001
    ..CONCLUSION: Clusterin was induced in glomerular mesangial cells during the course of immune-mediated injuries. This up-regulation of clusterin may play a critical role in protecting mesangial cells from complement attack...
  23. ncbi Cloning and characterization of a novel subunit of protein serine/threonine phosphatase 4 from mesangial cells
    T Wada
    Molecular and Cellular Nephrology, Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
    J Am Soc Nephrol 12:2601-8. 2001
    ..As PP4 is an essential protein for nucleation, growth, and stabilization of microtubules at centrosomes/spindle pole bodies during cell division, PP4(Rmeg) may play a role in regulation of mitosis in mesangial cells...
  24. ncbi Cobalt promotes angiogenesis via hypoxia-inducible factor and protects tubulointerstitium in the remnant kidney model
    Tetsuhiro Tanaka
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Lab Invest 85:1292-307. 2005
    ..Collectively, these findings demonstrate a renoprotective role of HIF through angiogenesis and provide a rationale for therapeutic approaches to target HIF for activation...
  25. ncbi Apolipoprotein E2/E5 variants in lipoprotein glomerulopathy recurred in transplanted kidney
    T Miyata
    Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
    J Am Soc Nephrol 10:1590-5. 1999
    ....
  26. ncbi Podocyte protection by darbepoetin: preservation of the cytoskeleton and nephrin expression
    N Eto
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Kidney Int 72:455-63. 2007
    ..Our study demonstrates that darbepoetin treatment ameliorates podocyte injury and decreases proteinuria by a direct effect on podocytes. This may be accomplished by maintenance of the actin cytoskeleton and nephrin expression...
  27. ncbi Induction of protective genes by cobalt ameliorates tubulointerstitial injury in the progressive Thy1 nephritis
    Tetsuhiro Tanaka
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Kidney Int 68:2714-25. 2005
    ..CONCLUSION: Maneuvers to activate HIF in the ischemic tubulointerstitium will be a new direction to future therapeutic strategies...
  28. ncbi Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats
    Takanori Kumagai
    Div of Nephrology and Endocrinology, Univ of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Am J Physiol Renal Physiol 296:F912-21. 2009
    ..In conclusion, glyoxalase I exerts renoprotective effects in renal I/R injury via a reduction in MG accumulation in tubular cells...
  29. ncbi Hypoxia in renal disease with proteinuria and/or glomerular hypertension
    Tetsuhiro Tanaka
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan
    Am J Pathol 165:1979-92. 2004
    ..We propose here a possible pathological tie between chronic tubulointerstitial hypoxia and progressive glomerular diseases...
  30. ncbi Increased susceptibility of decay-accelerating factor deficient mice to anti-glomerular basement membrane glomerulonephritis
    H Sogabe
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    J Immunol 167:2791-7. 2001
    ..These results support the conclusion that membrane C3 convertase inhibitors like DAF play a protective role in complement-mediated immune glomerular damage in vivo...
  31. ncbi [Mechanisms in remodeling of the kidney]
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine
    Nihon Rinsho 66:1696-700. 2008
    ..Development of therapeutic approaches targeting final common pathways will open a new avenue in management of patients with CKD...
  32. ncbi A mesangium-predominant gene, megsin, is a new serpin upregulated in IgA nephropathy
    T Miyata
    Molecular and Cellular Nephrology, Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259 1193, Japan
    J Clin Invest 102:828-36. 1998
    ..Here we report a new human mesangium-predominant gene that may function as an inhibitory serpin in normal and abnormal biological processes of glomerulus...
  33. ncbi Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient
    T Miyata
    Molecular and Cellular Nephrology, Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine, and Bohsei Hiratsuka Clinic, Kanagawa, Japan
    Kidney Int 60:2351-9. 2001
    ..Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification system of precursor reactive carbonyl compounds (RCOs) in the in vivo AGE formation...
  34. ncbi C6 mediates chronic progression of tubulointerstitial damage in rats with remnant kidneys
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    J Am Soc Nephrol 13:928-36. 2002
    ..Treatment to reduce C5b-9 attack in tubular cells may slow progression and facilitate recovery...
  35. ncbi Activation of the renin-angiotensin system and chronic hypoxia of the kidney
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Hypertens Res 31:175-84. 2008
    ..Chronic hypoxia in the kidney is an ideal therapeutic target, and the beneficial effects of blockade of RAS in kidney disease are, at least in part, mediated by the amelioration of local hypoxia. (Hypertens Res 2008; 31: 175-184)...
  36. ncbi Hypoperfusion of peritubular capillaries induces chronic hypoxia before progression of tubulointerstitial injury in a progressive model of rat glomerulonephritis
    Makiko Matsumoto
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    J Am Soc Nephrol 15:1574-81. 2004
    ..In conclusion, stagnation of blood flow in peritubular capillaries induced chronic hypoxia at an early stage in this model, which was followed by progressive tubulointerstitial injury and a loss of peritubular capillaries...
  37. ncbi Evidence of tubular hypoxia in the early phase in the remnant kidney model
    Krissanapong Manotham
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    J Am Soc Nephrol 15:1277-88. 2004
    ..The initial hypoxia in this model was dependent on activation of the renin-angiotensin system and hemodynamic alterations after nephron loss...
  38. ncbi Albumin induces endoplasmic reticulum stress and apoptosis in renal proximal tubular cells
    T Ohse
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Kidney Int 70:1447-55. 2006
    ..In conclusion, renal tubular cells exposed to high protein load suffer from ER stress. ER stress may subsequently lead to tubular damage by activation of caspase-12...
  39. ncbi Preconditioning with endoplasmic reticulum stress ameliorates mesangioproliferative glomerulonephritis
    Reiko Inagi
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1, Hongo Bunkyo ku, Tokyo 113 8655, Japan
    J Am Soc Nephrol 19:915-22. 2008
    ..These findings suggest the possibility of therapeutic approaches targeting ER stress in mesangioproliferative glomerulonephritis...
  40. ncbi Cytoglobin, a novel globin, plays an antifibrotic role in the kidney
    Imari Mimura
    Div of Nephrology and Endocrinology, Univ of Tokyo School of Medicine, 7 3 1, Hongo, Bunkyo ku, Tokyo, 113 8655, Japan
    Am J Physiol Renal Physiol 299:F1120-33. 2010
    ..Cygb might represent a good therapeutic target in chronic kidney disease...
  41. ncbi Contribution of T lymphocytes to rat renal ischemia/reperfusion injury
    Eisei Noiri
    Department of Nephrology and Endocrinology 107 Lab, Hemodialysis and Apheresis, University Hospital, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo, Japan
    Clin Exp Nephrol 13:25-32. 2009
    ..This study aimed to elucidate the early involvement of T lymphocytes in renal ischemia/reperfusion injury...
  42. ncbi In a type 2 diabetic nephropathy rat model, the improvement of obesity by a low calorie diet reduces oxidative/carbonyl stress and prevents diabetic nephropathy
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo
    Nephrol Dial Transplant 20:2661-9. 2005
    ..CONCLUSION: The present findings suggest a direct role of obesity in the generation of a localized oxidative stress and AGE formation, directly responsible for DN...
  43. ncbi The role of glyoxalase system in renal hypoxia
    Reiko Inagi
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Adv Exp Med Biol 662:49-55. 2010
    ..In conclusion, glyoxalase I has renoprotective effects in renal hypoxia such as I/R injury via a reduction in cytotoxic MG level in tubular cells...
  44. ncbi Clinical and psychological aspects of restless legs syndrome in uremic patients on hemodialysis
    Jiro Takaki
    Department of Psychosomatic Medicine, Tokyo University Hospital, Faculty of Medicine, University of Tokyo, Tokyo Japan
    Am J Kidney Dis 41:833-9. 2003
    ..The purpose of this study is to determine relationships of the presence of RLS in uremic patients regularly undergoing hemodialysis (HD) with demographic, clinical, and psychological factors...
  45. ncbi Transdifferentiation of cultured tubular cells induced by hypoxia
    Krissanapong Manotham
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Kidney Int 65:871-80. 2004
    ..Chronic ischemic kidney revealed in vivo tubular EMT at day 7. CONCLUSION: Hypoxia can induce tubular EMT. This process may play an important role in progression of kidney disease...
  46. ncbi Induction of renoprotective gene expression by cobalt ameliorates ischemic injury of the kidney in rats
    Makiko Matsumoto
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    J Am Soc Nephrol 14:1825-32. 2003
    ..HIF induction is one possible and attractive explanation for the observed effects...
  47. ncbi Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis
    Daisuke Son
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Am J Physiol Renal Physiol 294:F62-72. 2008
    ..This study, for the first time, uncovered maladaptive suppression of Cu/Zn-SOD as a mediator of a vicious cycle of oxidative stress and subsequent renal injury induced by chronic hypoxia...
  48. ncbi Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo
    Intern Med 43:9-17. 2004
    ..This induces chronic hypoxia in this compartment, rendering a vicious cycle. Development of novel therapeutic approaches against these final common pathways will enable us to target any types of renal disease...
  49. ncbi Hypoxia and expression of hypoxia-inducible factor in the aging kidney
    Tetsuhiro Tanaka
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
    J Gerontol A Biol Sci Med Sci 61:795-805. 2006
    ..These findings point to the involvement of hypoxia and highlight the pathological relevance of HIF and its target genes in the aging kidney...
  50. ncbi The role of hypoxia, increased oxygen consumption, and hypoxia-inducible factor-1 alpha in progression of chronic kidney disease
    Tetsuhiro Tanaka
    Division for Health Service Promotion, University of Tokyo, Bunkyo ku, Tokyo, Japan
    Curr Opin Nephrol Hypertens 19:43-50. 2010
    ..Tubulointerstitial hypoxia in the kidney has been considered a hallmark of injury and mediator of disease progression. This review focuses on hypoxia-inducible factor (HIF)-1, a master transcription factor in cellular adaptation to hypoxia...
  51. ncbi [Function and pathophysiology of renal tubulointerstitium]
    Daisuke Son
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine
    Nippon Rinsho 64:103-6. 2006
  52. ncbi Hypoxia-induced apoptosis in cultured glomerular endothelial cells: involvement of mitochondrial pathways
    Tetsuhiro Tanaka
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Kidney Int 64:2020-32. 2003
    ..Further investigation into glomerular endothelial cell injury and intracellular signaling in a hypoxic milieu is required to better understand and ultimately prevent progression of chronic kidney disease...
  53. ncbi Pathophysiological role of the glyoxalase system in renal hypoxic injury
    Takanori Kumagai
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Ann N Y Acad Sci 1126:265-7. 2008
    ..These results demonstrate that GLO I has renoprotective effects in I/R injury via reduction of protein modification by MG...
  54. ncbi Imbalance of T-cell subsets in angiotensin II-infused hypertensive rats with kidney injury
    Jing Shao
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    Hypertension 42:31-8. 2003
    ..The imbalance of Th subsets was associated with hypertensive kidney injury induced by Ang II. Some of the beneficial effects of ARBs might be explained by their immunomodulatory reactions...
  55. ncbi Novel serpinopathy in rat kidney and pancreas induced by overexpression of megsin
    Reiko Inagi
    Molecular and Cellular Nephrology, Institute of Medical Sciences, Tokai University, Kanagawa, Japan
    J Am Soc Nephrol 16:1339-49. 2005
    ..This model of serpinopathy is the first to involve the kidney and the pancreas...
  56. ncbi Anti-hypertensive agents inhibit in vivo the formation of advanced glycation end products and improve renal damage in a type 2 diabetic nephropathy rat model
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    J Am Soc Nephrol 14:1212-22. 2003
    ..It is concluded that AGE inhibition should be included in the therapeutic strategy of DN...
  57. ncbi Rationale and design of the Eplerenone combination Versus conventional Agents to Lower blood pressure on Urinary Antialbuminuric Treatment Effect (EVALUATE) trial: a double-blinded randomized placebo-controlled trial to evaluate the antialbuminuric effect
    Katsuyuki Ando
    Department of Nephrology and Endocrinology, Faculty of Medicine, University of Tokyo Hospital, Tokyo, Japan
    Hypertens Res 33:616-21. 2010
    ..This trial is expected to show whether a low dose of mineralocorticoid receptor antagonists can exert an antialbuminuric effect in patients with chronic kidney disease...
  58. ncbi Indoxyl sulfate inhibits proliferation of human proximal tubular cells via endoplasmic reticulum stress
    Takahisa Kawakami
    University of Tokyo School of Medicine, Japan
    Am J Physiol Renal Physiol 299:F568-76. 2010
    ..These are possible targets for suppressing progression of CKD...
  59. ncbi Efficient in vitro lowering of carbonyl stress by the glyoxalase system in conventional glucose peritoneal dialysis fluid
    Reiko Inagi
    Molecular and Cellular Nephrology, Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
    Kidney Int 62:679-87. 2002
    ..The clinical relevance of this approach is yet to be documented...
  60. ncbi Laboratory and imaging features of kidney involvement in autoimmune pancreatitis: incidence, correlation, and steroid therapy response
    H Nishi
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Clin Nephrol 73:253-9. 2010
    ....
  61. ncbi Drug discovery for overcoming chronic kidney disease (CKD): prolyl-hydroxylase inhibitors to activate hypoxia-inducible factor (HIF) as a novel therapeutic approach in CKD
    Tetsuhiro Tanaka
    Division of Nephrology and Endocrinology, University of Tokyo Hospital and School of Medicine, Tokyo, Japan
    J Pharmacol Sci 109:24-31. 2009
    ....
  62. ncbi The role of megsin, a serine protease inhibitor, in diabetic mesangial matrix accumulation
    Shuichi Ohtomo
    Institute of Medical Sciences, Tokai University, Kanagawa, Japan
    Kidney Int 74:768-74. 2008
    ..Our study suggests that the mesangial matrix accumulation caused by hyperglycemia in diabetes might be due at least in part to up-regulation of megsin which can inhibit plasmin and MMP activities...
  63. ncbi Hypoxia induces apoptosis in SV40-immortalized rat proximal tubular cells through the mitochondrial pathways, devoid of HIF1-mediated upregulation of Bax
    Tetsuhiro Tanaka
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1, Hongo, Bunkyo ku, Tokyo, Japan
    Biochem Biophys Res Commun 309:222-31. 2003
    ..These findings extend previous reports on hypoxia-mediated tubular cell apoptosis and demonstrate the possible involvement of HIF-1 as an upstream molecule of Bax...
  64. ncbi Protection of endothelial cells by dextran sulfate in rats with thrombotic microangiopathy
    Nobuaki Eto
    Division of Nephrology and Endocrinology, University of Tokyo, School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    J Am Soc Nephrol 16:2997-3005. 2005
    ..This protection may be mediated by DXS's binding directly to the surface of glomerular endothelium and amelioration of coagulation, complement activation, and cellular matrix loss...
  65. ncbi Hypoxia-inducible factor modulates tubular cell survival in cisplatin nephrotoxicity
    Tetsuhiro Tanaka
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan
    Am J Physiol Renal Physiol 289:F1123-33. 2005
    ..A possibility was suggested that activation of HIF-1 could be a new promising therapeutic target for hypoxic renal diseases...
  66. ncbi Protective role of hypoxia-inducible factor-2alpha against ischemic damage and oxidative stress in the kidney
    Ichiro Kojima
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    J Am Soc Nephrol 18:1218-26. 2007
    ..These results suggest that HIF-2alpha in the endothelium has a protective role against ischemia of the kidney via amelioration of oxidative stress...
  67. ncbi Hemoglobin is expressed by mesangial cells and reduces oxidant stress
    Hiroshi Nishi
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo, Japan
    J Am Soc Nephrol 19:1500-8. 2008
    ..In summary, Hb is expressed by rat mesangial cells, and its potential functions may include antioxidative defense...
  68. ncbi A biologic role of HIF-1 in the renal medulla
    Krissanapong Manotham
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    Kidney Int 67:1428-39. 2005
    ..However, a biologic role of HIF-1 in the medulla of the kidney, which is considered perpetually hypoxic under physiologic conditions due to its unique circulation, remains to be elucidated...
  69. ncbi Ultrapure dialysate decreases plasma pentosidine, a marker of "carbonyl stress"
    Yuko Izuhara
    Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan
    Am J Kidney Dis 43:1024-9. 2004
    ..CONCLUSION: Ultrapure dialysate reduces plasma pentosidine levels and improves plasma triglyceride levels in hemodialysis patients through still undefined mechanisms...
  70. ncbi Renoprotective properties of angiotensin receptor blockers beyond blood pressure lowering
    Yuko Izuhara
    Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan
    J Am Soc Nephrol 16:3631-41. 2005
    ..These benefits of ARB may contribute to the renoprotection observed beyond BP lowering...
  71. ncbi Overexpression of the serpin megsin induces progressive mesangial cell proliferation and expansion
    Toshio Miyata
    Molecular and Cellular Nephrology, Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan
    J Clin Invest 109:585-93. 2002
    ..Megsin therefore exerts a biologically relevant influence on mesangial function, and on the mesangial microenvironment, such that simple overexpression of this endogenous serpin engenders elementary mesangial lesions...
  72. ncbi Current issues and future perspectives of chronic renal failure
    Kiyoshi Kurokawa
    Medical Research Institute and Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
    J Am Soc Nephrol 13:S3-6. 2002
  73. ncbi In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage
    Haruo Mitani
    Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan
    Hypertension 39:838-43. 2002
    ....
  74. ncbi Novel therapeutic approach targeting the HIF-HRE system in the kidney
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Adv Exp Med Biol 645:81-6. 2009
    ..Current advance has elucidated the detailed mechanism of hypoxia-induced transcription, giving hope for the development of novel therapeutic approaches against hypoxia...
  75. ncbi Pyridoxamine improves functional, structural, and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats
    Takatoshi Kakuta
    Department of Internal Medicine and Institute of Medical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan
    Kidney Int 68:1326-36. 2005
    ....
  76. ncbi Endoplasmic reticulum stress induces autophagy in renal proximal tubular cells
    Takahisa Kawakami
    University of Tokyo School of Medicine, Japan
    Nephrol Dial Transplant 24:2665-72. 2009
    ..However, little information about autophagy in renal tubular cells is available. We investigated the relationship of autophagy with endoplasmic reticulum (ER) stress in proximal tubular cells...
  77. ncbi High glucose blunts vascular endothelial growth factor response to hypoxia via the oxidative stress-regulated hypoxia-inducible factor/hypoxia-responsible element pathway
    Pisut Katavetin
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    J Am Soc Nephrol 17:1405-13. 2006
    ..In conclusion, high glucose blunts VEGF response to hypoxia in IRPTC. This effect is mediated by the oxidative stress-regulated HIF-HRE pathway...
  78. ncbi [Progress in nephrology during this year: Basic research for kidney diseases]
    Masaomi Nangaku
    Nippon Jinzo Gakkai Shi 50:5-10. 2008
  79. ncbi Synergistic contributions of carbonyl stress and megsin in diabetic nephropathy
    Reiko Inagi
    Institute of Medical Sciences, Tokai University School of Medicine, Kanagawa 259-1193, Japan
    Ann N Y Acad Sci 1043:605-8. 2005
    ..Megsin and AGEs are suitable targets for new drugs of diabetic nephropathy and for the development of appropriate animal models of diabetic nephropathy...
  80. ncbi Possible mechanism for medial smooth muscle cell injury in diabetic nephropathy: glycoxidation-mediated local complement activation
    Noriko Uesugi
    Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan
    Am J Kidney Dis 44:224-38. 2004
    ..We focused on medial smooth muscle cell (SMC) injury and the involvement of glycoxidation and complement activation...
  81. ncbi Accelerated glomerular injury in hemi-nephrectomized transgenic mice of mesangial cell-predominant serpin, megsin
    Hiroshi Onogi
    Preventure Program, Office of Technology Transfer, Japan Science and Technology Cooperation, Tokyo, Japan
    Nephron Exp Nephrol 96:e127-33. 2004
    ..Megsin has thus a biologically relevant influence on the development of glomerular damage. The hemi-nephrectomized model of this transgenic mouse might serve as a tool to investigate the mechanisms of glomerular disease...
  82. ncbi Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model
    Shuichi Ohtomo
    Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa 259 1193, Japan
    Nephrol Dial Transplant 23:1166-72. 2008
    ..Cobalt enhances the activity of the hypoxia-inducible factor (HIF), a key factor in the defence against hypoxia. Its long-term effect on DN is evaluated...
  83. ncbi Establishment of a sandwich ELISA for human megsin, a kidney-specific serine protease inhibitor
    Reiko Inagi
    Institute of Medical Sciences, Tokai University School of Medicine, Isehara, Kanagawa 259 1193, Japan
    Nephrol Dial Transplant 22:3311-7. 2007
    ..Megsin expression is up-regulated in human and experimental renal diseases associated with mesangial proliferation and expansion, suggesting that urinary megsin may be a novel diagnostic marker for some renal diseases...
  84. ncbi The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease
    Hiroyuki Kobori
    Department of Medicine, Director of the Molecular Core in Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112 2699, USA
    Pharmacol Rev 59:251-87. 2007
    ..We will also discuss the impact of antihypertensive agents in preventing the progressive increases in the intrarenal RAS during the development of hypertension and renal injury...
  85. ncbi A novel class of advanced glycation inhibitors ameliorates renal and cardiovascular damage in experimental rat models
    Yuko Izuhara
    Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa 259 1193, Japan
    Nephrol Dial Transplant 23:497-509. 2008
    ..The hypotensive effects of ARBs', however, may limit their use. In the present study, we report the synthesis of a new AGE inhibitor, TM2002, and its effects in vitro and in vivo...
  86. ncbi Enhanced erythropoiesis mediated by activation of the renin-angiotensin system via angiotensin II type 1a receptor
    Hideki Kato
    Center for Tsukuba Advanced Research Alliance TARA, University of Tsukuba, Tsukuba, Ibaraki, Japan
    FASEB J 19:2023-5. 2005
    ..These results provide clear genetic evidence that activated RAS enhances erythropoiesis through the AT1a receptor of kidney cells and that this effect is mediated by the elevation of plasma erythropoietin levels in vivo...
  87. ncbi A novel class of prolyl hydroxylase inhibitors induces angiogenesis and exerts organ protection against ischemia
    Masaomi Nangaku
    Institute of Medical Sciences and Division of Nephrology, Hypertension and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa 259 1193, Japan
    Arterioscler Thromb Vasc Biol 27:2548-54. 2007
    ..Hypoxia inducible factor (HIF) plays a pivotal role in the adaptation to ischemic conditions. Its activity is modulated by an oxygen-dependent hydroxylation of proline residues by prolyl hydroxylases (PHD)...
  88. ncbi A novel Sartan derivative with very low angiotensin II type 1 receptor affinity protects the kidney in type 2 diabetic rats
    Yuko Izuhara
    Center for Translational and Advanced Research, Tohoku University Graduate School of Medicine, Sendai, Japan
    Arterioscler Thromb Vasc Biol 28:1767-73. 2008
    ..Antihypertensive angiotensin II receptor blockers (ARBs) protect the kidney, at least in part, independently of blood pressure lowering. Still, the extent to which blood pressure lowering is related to renoprotection remains unclear...
  89. ncbi Mesangial cell-predominant functional gene, megsin
    Reiko Inagi
    Institute of Medical Sciences, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259 1193, Japan
    Clin Exp Nephrol 7:87-92. 2003
    ..Identification of the exact biological functions and target proteases of megsin will lead us to develop novel therapeutic approaches to glomerular diseases...
  90. ncbi [Tubulointerstitial disorders and factors influencing the etiological mechanism]
    Tetsuhiro Tanaka
    Nippon Naika Gakkai Zasshi 92:2042-6. 2003
  91. ncbi Mesangial cell-predominant gene, megsin
    Reiko Inagi
    Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan
    Nephrol Dial Transplant 17:32-3. 2002
    ..Genetic manipulation of megsin engenders two elementary mesangial lesions, mesangial expansion and an increase in the number of mesangial cells...
  92. ncbi Anti-carbonic anhydrase II antibody in autoimmune pancreatitis and tubulointerstitial nephritis
    Hiroshi Nishi
    Nephrol Dial Transplant 22:1273-5. 2007
  93. ncbi Inhibition of plasminogen activator inhibitor-1: its mechanism and effectiveness on coagulation and fibrosis
    Yuko Izuhara
    Institute of Medical Sciences, Tokai University, Kanagawa, Japan
    Arterioscler Thromb Vasc Biol 28:672-7. 2008
    ..For the first time, we apply a new approach of virtual screening to discover novel, orally active, small molecule serpin inhibitors and report their effectiveness...