 |
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
|
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
BASIC SCIENCE |
*Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan; Department of Urology, Nagoya University School of Medicine, Nagoya, Japan; Institute of Medical Sciences, Tokai University School of Medicine, Kanagawa, Japan.
Correspondence to Dr. Masaomi Nangaku, Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan. Phone: 81-3-5800-8648; Fax: 81-3-5800-8806; E-mail: mnangaku-tky{at}umin.ac.jp
ABSTRACT. Chronic hypoxia likely plays a pivotal role in chronic renal disease, but the specifics of its involvement remain unclear. To elucidate how chronic hypoxia occurs and whether hypoxia participates in the progression of renal disease, the authors established an irreversible glomerulonephritis model induced by uninephrectomy and repeated anti-Thy-1 antibody injections. Glomerulosclerosis with microvascular obliteration was complete at 2 wk after antibody injection and was not restored until 11 wk. Tubulointerstitial injury was mild at 2 wk and was gradually exacerbated until 11 wk, a pattern that was in accordance with the loss of peritubular capillaries. Immunohistochemical analysis using pimonidazole revealed the augmentation of hypoxia in the cortex before the aggravation of tubulointerstitial injury and subsequent peritubular capillary loss. The preexistence of hypoxia implies that it had substantial participation in the progression of tubulointerstitial injury. To test whether blood flow was inhibited in diseased kidneys, capillaries with intact blood flow were identified by tail vein injection of biotinylated lectin specific to endothelial cells. The renal microvasculature was well recognized by lectin in the controls, whereas lectin binding to peritubular capillaries was strikingly decreased in diseased kidneys, suggesting a disturbance of blood flow. Intravital microscopy analysis confirmed that blood flow in peritubular capillaries was decreased by approximately 40% in the disease group compared with the controls. 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.
This article has been cited by other articles:
 |
|
 |
|
  R. G. Evans, B. S. Gardiner, D. W. Smith, and P. M. O'Connor Intrarenal oxygenation: unique challenges and the biophysical basis of homeostasis Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1259 - F1270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Ferraccioli and G Romano Renal interstitial cells, proteinuria and progression of lupus nephritis: new frontiers for old factors Lupus, June 1, 2008; 17(6): 533 - 540. [Abstract] [PDF]
|
|
|
|
 |
|
 M. G. Wong, Y. Suzuki, C. Tanifuji, H. Akiba, K. Okumura, T. Sugaya, T. Yamamoto, S. Horikoshi, S. Y. Tan, C. Pollock, et al. Peritubular Ischemia Contributes More to Tubular Damage than Proteinuria in Immune-Mediated Glomerulonephritis J. Am. Soc. Nephrol., February 1, 2008; 19(2): 290 - 297. [Full Text] [PDF]
|
|
|
|
|
|
C. Temm and J. H. Dominguez Microcirculation: nexus of comorbidities in diabetes Am J Physiol Renal Physiol, August 1, 2007; 293(2): F486 - F493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Meier, J. Rossert, P.-F. Plouin, and M. Burnier Atherosclerotic renovascular disease: beyond the renal artery stenosis Nephrol. Dial. Transplant., April 1, 2007; 22(4): 1002 - 1006. [Full Text] [PDF]
|
|
|
|
|
|
L. Wu, M. M. Tiwari, K. J. Messer, J. H. Holthoff, N. Gokden, R. W. Brock, and P. R. Mayeux Peritubular capillary dysfunction and renal tubular epithelial cell stress following lipopolysaccharide administration in mice Am J Physiol Renal Physiol, January 1, 2007; 292(1): F261 - F268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ding, S. Cui, C. Li, S. Jothy, V. Haase, B. Steer, P. Marsden, J. Pippin, S. Shankland, M. Rastaldi, et al. Faulty Podocyte Hypoxia Sensing--A Novel Pathway for Rapidly Progressive Glomerulonephritis: Loss of the Tumor Suppressor Vhlh Leads to Upregulation of Cxcr4 and Rapidly Progressive Glomerulonephritis. Nat Med 12: 1081-1087, 2006 J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3267 - 3272. [Full Text] [PDF]
|
|
|
|
|
|
V. H. Haase Hypoxia-inducible factors in the kidney Am J Physiol Renal Physiol, August 1, 2006; 291(2): F271 - F281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kondo, H. Kiyomoto, T. Yamamoto, A. Miyatake, G.-P. Sun, M. Rahman, H. Hitomi, K. Moriwaki, T. Hara, S. Kimura, et al. Effects of Calcium Channel Blockade on Angiotensin II-Induced Peritubular Ischemia in Rats J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1047 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nangaku Chronic Hypoxia and Tubulointerstitial Injury: A Final Common Pathway to End-Stage Renal Failure J. Am. Soc. Nephrol., January 1, 2006; 17(1): 17 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tomita, H. Sogabe, S. Nakazato, S. Nakatsuji, T. Noto, K. Hamada, H. Kawachi, F. Shimizu, M. Matsuo, and S. Mutoh Monoclonal antibody 1-22-3-induced glomerulonephritis in uninephrectomized rats as a model of progressive renal failure Nephrol. Dial. Transplant., November 1, 2005; 20(11): 2358 - 2367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Saemann, T Weichhart, M Zeyda, G Staffler, M Schunn, K. Stuhlmeier, Y Sobanov, T. Stulnig, S Akira, A von Gabain, et al. Immunoregulation in Urinary Tract Inflammation--A Role of Tamm-Horsfall Glycoprotein: Tamm-Horsfall Glycoprotein Links Innate Immune Cell Activation with Adaptive Immunity via a Toll-Like Receptor-4-Dependent Mechanism. J Clin Invest 115: 468-475, 2005 J. Am. Soc. Nephrol., April 1, 2005; 16(4): 829 - 836. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tanaka, T. Miyata, R. Inagi, T. Fujita, and M. Nangaku Hypoxia in Renal Disease with Proteinuria and/or Glomerular Hypertension Am. J. Pathol., December 1, 2004; 165(6): 1979 - 1992. [Abstract] [Full Text] [PDF]
|
|
|
HOME
CURRENT ISSUE
ARCHIVES
JASN Express
ONLINE SUBMISSION
AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP |
Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673
