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Author Notes:
Correspondence to: Jennifer L. GOOCH, Ph.D., Medicine/Nephrology, Emory University School of Medicine, 101 Woodruff Circle, WMB 338, Atlanta, GA 30322, USA. Tel.: (404) 727-2525 Fax: (404) 727-3425 E-mail: jgooch@emory.edu
The authors do not have any competing financial interests.
Subject:
Research Funding:
Funding for this project was provided by the American Physiological Society STEP-UP program (MW), National Institutes of Health/NIDDK T32 DK00756 (CRW and BMW), National Institutes of Health R01 DK-085097 and Research Service, Atlanta VA Medical Center (RSH), and the Department of Veterans Affairs MERIT program (JLG).
Keywords:
- Science & Technology
- Life Sciences & Biomedicine
- Cell Biology
- Medicine, Research & Experimental
- Research & Experimental Medicine
- renal hypertrophy
- cyclosporin
- calcineurin
- uninephrectomy
- NFAT
- INDUCED CARDIAC-HYPERTROPHY
- GROWTH-FACTOR-BETA
- A-BETA
- DEPENDENT MECHANISM
- DIABETIC KIDNEY
- CYCLOSPORINE-A
- NADPH OXIDASE
- ALPHA-ISOFORM
- EXPRESSION
- MICE
Compensatory renal hypertrophy following uninephrectomy is calcineurin-independent
Abstract:
Calcineurin is a calcium-dependent phosphatase that is involved in many cellular processes including hypertrophy. Inhibition or genetic loss of calcineurin blocks pathological cardiac hypertrophy and diabetic renal hypertrophy. However, calcineurin does not appear to be involved in physiological cardiac hypertrophy induced by exercise. The role of calcineurin in a compensatory, non-pathological model of renal hypertrophy has not been tested. Therefore, in this study, we examined activation of calcineurin and the effect of calcineurin inhibition or knockout on compensatory hypertrophy following uninephrectomy (UNX). UNX induces ~15% increase in the size of the remaining kidney; the data show no change in the generation of reactive oxygen species (ROS), Nox4 or transforming growth factor-β expression confirming the model as one of compensatory hypertrophy. Next, analyses of the remaining kidney reveal that total calcineurin activity is increased, and, to a lesser extent, transcriptional activity of the calcineurin substrate nuclear factor of activated T cell is up-regulated following UNX. However, inhibition of calcineurin with cyclosporine failed to prevent compensatory renal hypertrophy. Likewise, hypertrophy was comparable to WT in mice lacking either isoform of the catalytic subunit of calcineurin (CnAα-/- or CnAβ-/-). In conclusion, similar to its role in the heart, calcineurin is required for pathological but not compensatory renal hypertrophy. This separation of signalling pathways could therefore help further define key factors necessary for pathological hypertrophy including diabetic nephropathy.
Copyright information:
© 2014 The Authors.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License ( http://creativecommons.org/licenses/by/3.0/), which permits distribution, public display, and publicly performance, making multiple copies, distribution of derivative works, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.
