AJP - Renal Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (September 11, 2002). doi:10.1152/ajprenal.00158.2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/1/F144    most recent
00158.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gooch, J. L.
Right arrow Articles by Abboud, H. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gooch, J. L.
Right arrow Articles by Abboud, H. E.

Articles in PresS, published online ahead of print September 11, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00158.2002
Submitted on April 25, 2002
Accepted on August 28, 2002

Calcineurin phosphatase is activated in diabetes and is required for glomerular hypertrophy and extracellular matrix accumulation

Jennifer L. Gooch1*, Jeffrey L. Barnes1, Sergio Garcia1, and Hanna E. Abboud1

1 Department of Medicine and Nephrology, University of Texas Health Science Center, San Antonio, San Antonio, TX, USA; Audie Murphy Division, South Texas Veterans Health Care System, San Antonio, TX, USA

* To whom correspondence should be addressed. E-mail: Gooch{at}uthscsa.edu.

Diabetic nephropathy is characterized by the rapid onset of hypertrophy and extracellular matrix (ECM) expansion. Previously, we showed that calcineurin phosphatase is required for hypertrophy and ECM synthesis in cultured mesangial cells. Therefore, we examined the effect of calcineurin inhibition on renal hypertrophy and ECM accumulation in streptozotocin (STZ)-induced diabetic rats. After 2 weeks of diabetes, calcineurin protein was increased in whole cortex and glomeruli in conjunction with increased phosphatase activity. Daily administration of cyclosporin A blocked both accumulation of calcineurin protein and calcineurin activity. Also associated with calcineurin up-regulation was nuclear localization of the calcineurin substrate NFATc1. Inhibition of calcineurin reduced whole kidney hypertrophy and abolished glomerular hypertrophy in diabetic rats. Furthermore, calcineurin inhibition substantially reduced ECM accumulation in diabetic glomeruli but not in cortical tissue, suggesting a differential effect of calcineurin inhibition in glomerular versus extra-glomerular tissue. Corresponding increases in fibronectin mRNA and TGFß mRNA were observed in tubulointerstitium but not in glomeruli. In summary, calcineurin plays an important role in glomerular hypertrophy and ECM accumulation in diabetic nephropathy.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
N. A. Bobadilla and G. Gamba
New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone
Am J Physiol Renal Physiol, July 1, 2007; 293(1): F2 - F9.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. Doller, E.-S. Akool, R. Muller, P. Gutwein, C. Kurowski, J. Pfeilschifter, and W. Eberhardt
Molecular Mechanisms of Cyclosporin A Inhibition of the Cytokine-Induced Matrix Metalloproteinase-9 in Glomerular Mesangial Cells
J. Am. Soc. Nephrol., February 1, 2007; 18(2): 581 - 592.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J. L. Gooch, R. L. Guler, J. L. Barnes, and J. J. Toro
Loss of calcineurin A{alpha} results in altered trafficking of AQP2 and in nephrogenic diabetes insipidus
J. Cell Sci., June 15, 2006; 119(12): 2468 - 2476.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. L. Gooch
An emerging role for calcineurin A{alpha} in the development and function of the kidney
Am J Physiol Renal Physiol, April 1, 2006; 290(4): F769 - F776.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
T. Oka, Y.-S. Dai, and J. D. Molkentin
Regulation of Calcineurin through Transcriptional Induction of the calcineurin A{beta} Promoter In Vitro and In Vivo
Mol. Cell. Biol., August 1, 2005; 25(15): 6649 - 6659.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
J. Minguillon, B. Morancho, S.-J. Kim, M. Lopez-Botet, and J. Aramburu
Concentrations of cyclosporin A and FK506 that inhibit IL-2 induction in human T cells do not affect TGF-{beta}1 biosynthesis, whereas higher doses of cyclosporin A trigger apoptosis and release of preformed TGF-{beta}1
J. Leukoc. Biol., May 1, 2005; 77(5): 748 - 758.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
D. L. Lee, J. M. Sasser, J. L. Hobbs, A. Boriskie, D. M. Pollock, P. K. Carmines, and J. S. Pollock
Posttranslational regulation of NO synthase activity in the renal medulla of diabetic rats
Am J Physiol Renal Physiol, January 1, 2005; 288(1): F82 - F90.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. L. Gooch, J. J. Toro, R. L. Guler, and J. L. Barnes
Calcineurin A-{alpha} But Not A-{beta} Is Required for Normal Kidney Development and Function
Am. J. Pathol., November 1, 2004; 165(5): 1755 - 1765.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. L. Gooch, P. E. Pergola, R. L. Guler, H. E. Abboud, and J. L. Barnes
Differential Expression of Calcineurin A Isoforms in the Diabetic Kidney
J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1421 - 1429.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.