Journal of the American Society of Nephrology
2007 JASN IMPACT FACTOR 7.111 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by DIXON, R.
Right arrow Articles by BRUNSKILL, N. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by DIXON, R.
Right arrow Articles by BRUNSKILL, N. J.
J Am Soc Nephrol 10:1487-1497, 1999
© 1999 American Society of Nephrology

REGULAR ARTICLES

Activation of Mitogenic Pathways by Albumin in Kidney Proximal Tubule Epithelial Cells

Implications for the Pathophysiology of ProteinuricStates

RICK DIXON* and NIGEL JOHN BRUNSKILL*,{dagger}

* Department of Cell Physiology and Pharmacology, Leicester University School of Medicine, Leicester, United Kingdom.
{dagger} Department of Nephrology, Leicester University School of Medicine, Leicester, United Kingdom.

Correspondence to Dr. Nigel Brunskill, Department of Cell Physiology and Pharmacology, University of Leicester, P.O. Box 138, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, United Kingdom. Phone: 44 116 252 3078; Fax: 44 116 252 5045; E-mail: njb18{at}le.ac.uk

Abstract. Albumin is filtered into the proximal tubule in large quantities in nephrotic states. It has been proposed that this protein may have a toxic effect on tubular epithelial cells and may be responsible for the initiation of interstitial inflammation and scarring. The mitogenic effect of recombinant human albumin in wild-type opossum kidney cells and in similar cells transfected with a dominant negative p85 subunit ({Delta}p85) of phopshatidylinositide 3-kinase (PI 3-kinase) has been studied. This study demonstrates that recombinant human albumin stimulates proliferation of opossum kidney cells in culture. This effect is mediated via PI 3-kinase, and is inhibited by wortmannin and {Delta}p85 expression. Albumin stimulates PI 3-kinase activity in opossum kidney cells as determined by three different experimental procedures. Recombinant albumin also stimulates pp70s6 kinase activity in a kinase cascade downstream of PI 3-kinase. Activity of pp70s6 kinase is essential for albumin-induced proliferation of opossum kidney cells. It is proposed that this mitogenic pathway may have a critical role in proximal tubular homeostasis and pathophysiology of proteinuric states.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
Y. Urahama, Y. Ohsaki, Y. Fujita, S. Maruyama, Y. Yuzawa, S. Matsuo, and T. Fujimoto
Lipid Droplet-Associated Proteins Protect Renal Tubular Cells from Fatty Acid-Induced Apoptosis
Am. J. Pathol., November 1, 2008; 173(5): 1286 - 1294.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
F. Theilig, W. Kriz, T. Jerichow, P. Schrade, B. Hahnel, T. Willnow, M. Le Hir, and S. Bachmann
Abrogation of Protein Uptake through Megalin-Deficient Proximal Tubules Does Not Safeguard against Tubulointerstitial Injury
J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1824 - 1834.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
E. Erkan, P. Devarajan, and G. J. Schwartz
Mitochondria Are the Major Targets in Albumin-Induced Apoptosis in Proximal Tubule Cells
J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1199 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
L. Schaefer, W. Tsalastra, A. Babelova, M. Baliova, J. Minnerup, L. Sorokin, H.-J. Grone, D. P. Reinhardt, J. Pfeilschifter, R. V. Iozzo, et al.
Decorin-Mediated Regulation of Fibrillin-1 in the Kidney Involves the Insulin-Like Growth Factor-I Receptor and Mammalian Target of Rapamycin
Am. J. Pathol., January 1, 2007; 170(1): 301 - 315.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
N. J. Brunskill
Rapamycin: A New String to the Antiproteinuric Bow?
J. Am. Soc. Nephrol., July 1, 2005; 16(7): 1878 - 1879.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. Gekle, K. Volker, S. Mildenberger, R. Freudinger, G. E. Shull, and M. Wiemann
NHE3 Na+/H+ exchanger supports proximal tubular protein reabsorption in vivo
Am J Physiol Renal Physiol, September 1, 2004; 287(3): F469 - F473.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
N. J. Brunskill
Albumin Signals the Coming of Age of Proteinuric Nephropathy
J. Am. Soc. Nephrol., February 1, 2004; 15(2): 504 - 505.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
H. Schmid, A. Henger, C. D. Cohen, K. Frach, H.-J. Grone, D. Schlondorff, and M. Kretzler
Gene Expression Profiles of Podocyte-Associated Molecules as Diagnostic Markers in Acquired Proteinuric Diseases
J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2958 - 2966.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
E. M. Lee, C. A. Pollock, K. Drumm, J. A. Barden, and P. Poronnik
Effects of pathophysiological concentrations of albumin on NHE3 activity and cell proliferation in primary cultures of human proximal tubule cells
Am J Physiol Renal Physiol, October 1, 2003; 285(4): F748 - F757.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
C. Zoja, M. Morigi, and G. Remuzzi
Proteinuria and Phenotypic Change of Proximal Tubular Cells
J. Am. Soc. Nephrol., June 1, 2003; 14(90001): S36 - 41.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. Arici, R. Chana, A. Lewington, J. Brown, and N. J. Brunskill
Stimulation of Proximal Tubular Cell Apoptosis by Albumin-Bound Fatty Acids Mediated by Peroxisome Proliferator Activated Receptor-{gamma}
J. Am. Soc. Nephrol., January 1, 2003; 14(1): 17 - 27.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
M. Arici, J. Brown, M. Williams, K. P. G. Harris, J. Walls, and N. J. Brunskill
Fatty acids carried on albumin modulate proximal tubular cell fibronectin production: a role for protein kinase C
Nephrol. Dial. Transplant., October 1, 2002; 17(10): 1751 - 1757.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. E. Thomas, K. P. G. Harris, J. Walls, P. N. Furness, and N. J. Brunskill
Fatty acids exacerbate tubulointerstitial injury in protein-overload proteinuria
Am J Physiol Renal Physiol, October 1, 2002; 283(4): F640 - F647.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
K. Morrisey, R. A. Evans, L. Wakefield, and A. O. Phillips
Translational Regulation of Renal Proximal Tubular Epithelial Cell Transforming Growth Factor-{beta}1 Generation by Insulin
Am. J. Pathol., November 1, 2001; 159(5): 1905 - 1915.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
A. J. P. Lewington, M. Arici, K. P. G. Harris, N. J. Brunskill, and J. Walls
Modulation of the renin-angiotensin system in proteinuric renal disease: are there added benefits?
Nephrol. Dial. Transplant., May 1, 2001; 16(5): 885 - 888.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
N. Obermuller, B. Kranzlin, W. F. Blum, N. Gretz, and R. Witzgall
An endocytosis defect as a possible cause of proteinuria in polycystic kidney disease
Am J Physiol Renal Physiol, February 1, 2001; 280(2): F244 - F253.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
N. J. Brunskill
Albumin and proximal tubular cells--beyond endocytosis
Nephrol. Dial. Transplant., November 1, 2000; 15(11): 1732 - 1734.
[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