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 (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 Maeshima, Y.
Right arrow Articles by Ota, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maeshima, Y.
Right arrow Articles by Ota, Z.

Journal of the American Society of Nephrology, Vol 7, 2219-2229, Copyright © 1996 by American Society of Nephrology

REGULAR ARTICLES

Antisense oligonucleotides to proliferating cell nuclear antigen and Ki- 67 inhibit human mesangial cell proliferation

Y Maeshima, N Kashihara, H Sugiyama, H Makino and Z Ota
Third Department of Internal Medicine, Okayama University Medical School, Japan.

Proliferating cell nuclear antigen (PCNA) and Ki-67 are cell cycle- associated nuclear proteins and are used as markers for proliferating cells. This study attempted to inhibit glomerular mesangial cell (MC) proliferation, which is the hallmark of many forms of glomerular disease, by inhibiting these nuclear proteins with antisense oligodeoxynucleotides. The antisense and sense phosphorothioate oligodeoxynucleotides complementary to PCNA and Ki-67 mRNA, including the initiation codon, were synthesized. Human MC were cultured in growth medium in the presence of sense or antisense oligodeoxynucleotides, and the effects of these oligodeoxynucleotides on mesangial cell proliferation were evaluated by direct cell count. Both PCNA and Ki-67 antisense oligodeoxynucleotides significantly inhibited mesangial cell proliferation as compared with sense oligodeoxynucleotides. Antisense oligodeoxynucleotides (10 microM) for PCNA and Ki-67 inhibited mesangial cell growth by greater than 50%. The effect of antisense oligodeoxynucleotides on target protein expression was examined by immunocytochemistry using specific monoclonal antibodies. Reverse transcription-polymerase chain reaction also was performed to evaluate the effect of antisense oligodeoxynucleotides on PCNA and Ki-67 mRNA expression. Studies of target protein and mRNA expression revealed that the inhibitory effects of the antisense oligonucleotides were mediated through decreases in the expression of both mRNA and protein. Sense oligodeoxynucleotides produced little effect. These results indicate that antisense oligodeoxynucleotides targeting PCNA and Ki-67 mRNA reduce the expression of these gene products and inhibit mesangial cell proliferation. Moreover, these results suggest the feasibility of antisense strategies designed to inhibit PCNA and Ki-67 expression for the inhibition of mesangial cell proliferation in vivo.


This article has been cited by other articles:


Home page
 ChestHome page
J. Gray, J. T. Mao, E. Szabo, M. Kelley, J. Kurie, and G. Bepler
Lung Cancer Chemoprevention: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)
Chest, September 1, 2007; 132(3_suppl): 56S - 68S.
[Abstract] [Full Text] [PDF]

Home page
 Poult. Sci.Home page
M. Inafuku, T. Toda, T. Okabe, A. Shinjo, H. Iwasaki, and H. Oku
Expression of Cell-Cycle-Regulating Genes in the Development of Atherosclerosis in Japanese Quail (Coturnix japonica)
Poult. Sci., June 1, 2007; 86(6): 1166 - 1173.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Kontopidis, S.-Y. Wu, D. I. Zheleva, P. Taylor, C. McInnes, D. P. Lane, P. M. Fischer, and M. D. Walkinshaw
From the Cover: Structural and biochemical studies of human proliferating cell nuclear antigen complexes provide a rationale for cyclin association and inhibitor design
PNAS, February 8, 2005; 102(6): 1871 - 1876.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. Zeisberg, C. Bottiglio, N. Kumar, Y. Maeshima, F. Strutz, G. A. Muller, and R. Kalluri
Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models
Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1060 - F1067.
[Abstract] [Full Text]

Home page
 J. Am. Soc. Nephrol.Home page
S. LANG, A. HARTNER, R. B. STERZEL, and H. O. SCHÖCKLMANN
Requirement of Cyclin D1 in Mesangial Cell Mitogenesis
J. Am. Soc. Nephrol., August 1, 2000; 11(8): 1398 - 1408.
[Abstract] [Full Text]

Home page
 CirculationHome page
A. Frimerman, P. J. Welch, X. Jin, N. Eigler, S. Yei, J. Forrester, H. Honda, R. Makkar, J. Barber, and F. Litvack
Chimeric DNA-RNA Hammerhead Ribozyme to Proliferating Cell Nuclear Antigen Reduces Stent-Induced Stenosis in a Porcine Coronary Model
Circulation, February 9, 1999; 99(5): 697 - 703.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Maeshima, P. C. Colorado, A. Torre, K. A. Holthaus, J. A. Grunkemeyer, M. B. Ericksen, H. Hopfer, Y. Xiao, I. E. Stillman, and R. Kalluri
Distinct Antitumor Properties of a Type IV Collagen Domain Derived from Basement Membrane
J. Biol. Chem., July 7, 2000; 275(28): 21340 - 21348.
[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