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 Fan, Y.-p.
Right arrow Articles by Weiss, R. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fan, Y.-p.
Right arrow Articles by Weiss, R. H.
J Am Soc Nephrol 15:575-584, 2004
© 2004 American Society of Nephrology

BASIC SCIENCE

Exogenous Attenuation of p21Waf1/Cip1 Decreases Mesangial Cell Hypertrophy as a Result of Hyperglycemia and IGF-1

Ya-ping Fan* and Robert H. Weiss*,{dagger},{ddagger}

*Division of Nephrology, Department of Internal Medicine and {dagger}Cancer Center, University of California, Davis, California; and {ddagger}Department of Veterans’ Affairs Northern California Health Care System, Mather, California

Correspondence to Dr. Robert H. Weiss, Division of Nephrology, TB 136, Department of Internal Medicine, University of California, Davis, CA 95616. Phone: 530-752-4010; Fax: 530-752-3791; E-mail: rhweiss{at}ucdavis.edu

ABSTRACT. Renal mesangial cell hypertrophy is a characteristic of diabetic nephropathy as well as a response to renal stress or injury. Because hypertrophy is a result of increased protein content per cell without DNA replication, those proteins that control the cell cycle, such as the cyclin kinase inhibitor p21, represent fertile ground for studying the mechanism of this structural alteration. A key role for p21 in promoting mesangial cell (MC) hypertrophy has been established using p21 knockout mouse models. Furthermore, some of the biologic effects of IGF-1, including cell proliferation, have been shown to be positively influenced by p21. In an attempt to begin to translate these findings ultimately to the bedside, methods to attenuate p21 levels in wild-type kidney cells were examined. With the use of a phosphorothioated antisense oligodeoxynucleotide (ODN) to p21, which has previously been shown to decrease specifically and effectively p21 protein levels in a variety of cell types, it is shown that attenuation of p21 in MC leads to a dose-dependent reduction of hypertrophy in the milieu of hyperglycemic culture media. Furthermore, the hypertrophic effect of the IGF-1 on MC is also attenuated using the same antisense p21 ODN. There was no evidence of apoptosis or other toxicity in MC transfected with the concentrations of antisense p21 ODN used in these experiments. Because the use of antisense ODN in human disease is already established in other medical disciplines, the stage is now set for the use of antisense p21 ODN to attenuate renal cell hypertrophy in vivo, leading to a new strategy for treatment of diabetic nephropathy and other diseases characterized by MC hypertrophy.




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
B.-C. Yu, C.-K. Chang, H.-Y. Ou, K.-C. Cheng, and J.-T. Cheng
Decrease of peroxisome proliferator-activated receptor delta expression in cardiomyopathy of streptozotocin-induced diabetic rats
Cardiovasc Res, October 1, 2008; 80(1): 78 - 87.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
N. Lloberas, J. M. Cruzado, M. Franquesa, I. Herrero-Fresneda, J. Torras, G. Alperovich, I. Rama, A. Vidal, and J. M. Grinyo
Mammalian Target of Rapamycin Pathway Blockade Slows Progression of Diabetic Kidney Disease in Rats
J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1395 - 1404.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
K. Hiromura and S. J. Shankland
Negatively Regulating the Cell Cycle Can Be Positive
J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1361 - 1362.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
S. V. Griffin and S. J. Shankland
Not Just an Inhibitor: A Role for p21 Beyond The Cell Cycle--"The Truth Is Rarely Pure and Never Simple"
J. Am. Soc. Nephrol., March 1, 2004; 15(3): 825 - 826.
[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