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Calcineurin A-β is required for hypertrophy but not matrix expansion in the diabetic kidney.

Reddy RN, Knotts TL, Roberts BR, Molkentin JD, Price SR, Gooch JL - J. Cell. Mol. Med. (2011)

Bottom Line: The absence of β produced a significant decrease in total calcineurin activity in the inner medulla (IM) and reduced nuclear factor of activated T-cells (NFATc) activity.In conclusion, loss of the β isoform of calcineurin is sufficient to reproduce beneficial aspects of cyclosporine on diabetic renal hypertrophy but not matrix expansion.Therefore, while multiple signals appear to regulate matrix, calcineurin β appears to be a central mechanism involved in organ hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine/Division of Nephrology, Emory University School of Medicine, Atlanta, GA 30322, USA.

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Related in: MedlinePlus

Diabetic glomerular hypertrophy is attenuated by loss of calcineurin β. (A) Kidney sections were obtained from wild-type and β−/− control and diabetic mice, fixed, sectioned and then prepared with silver stain. Sections were then imaged with light microscopy and representative images from 6 week control and diabetic wild-type (i,ii) and β−/− mice (iii, iv) are shown. (B) Glomerular sizes were quantitated from kidney sections prepared as described in (A) using ImagePro Software (Media Cybernetics). Data shown are the mean ± S.E.M. of six mice per group. *P< 0.05, **P< 0.01, two-way anova.
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fig06: Diabetic glomerular hypertrophy is attenuated by loss of calcineurin β. (A) Kidney sections were obtained from wild-type and β−/− control and diabetic mice, fixed, sectioned and then prepared with silver stain. Sections were then imaged with light microscopy and representative images from 6 week control and diabetic wild-type (i,ii) and β−/− mice (iii, iv) are shown. (B) Glomerular sizes were quantitated from kidney sections prepared as described in (A) using ImagePro Software (Media Cybernetics). Data shown are the mean ± S.E.M. of six mice per group. *P< 0.05, **P< 0.01, two-way anova.

Mentions: Next, glomerular hypertrophy was examined. As expected, the size of glomeruli significantly increased in wild-type mice after 6 weeks of diabetes (there was no change in glomerular hypertrophy after 1 week [data not shown]). Similar to results from analysis of whole kidney hypertrophy, glomerular hypertrophy was attenuated in β−/− diabetic mice (Fig. 6A and B).


Calcineurin A-β is required for hypertrophy but not matrix expansion in the diabetic kidney.

Reddy RN, Knotts TL, Roberts BR, Molkentin JD, Price SR, Gooch JL - J. Cell. Mol. Med. (2011)

Diabetic glomerular hypertrophy is attenuated by loss of calcineurin β. (A) Kidney sections were obtained from wild-type and β−/− control and diabetic mice, fixed, sectioned and then prepared with silver stain. Sections were then imaged with light microscopy and representative images from 6 week control and diabetic wild-type (i,ii) and β−/− mice (iii, iv) are shown. (B) Glomerular sizes were quantitated from kidney sections prepared as described in (A) using ImagePro Software (Media Cybernetics). Data shown are the mean ± S.E.M. of six mice per group. *P< 0.05, **P< 0.01, two-way anova.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822805&req=5

fig06: Diabetic glomerular hypertrophy is attenuated by loss of calcineurin β. (A) Kidney sections were obtained from wild-type and β−/− control and diabetic mice, fixed, sectioned and then prepared with silver stain. Sections were then imaged with light microscopy and representative images from 6 week control and diabetic wild-type (i,ii) and β−/− mice (iii, iv) are shown. (B) Glomerular sizes were quantitated from kidney sections prepared as described in (A) using ImagePro Software (Media Cybernetics). Data shown are the mean ± S.E.M. of six mice per group. *P< 0.05, **P< 0.01, two-way anova.
Mentions: Next, glomerular hypertrophy was examined. As expected, the size of glomeruli significantly increased in wild-type mice after 6 weeks of diabetes (there was no change in glomerular hypertrophy after 1 week [data not shown]). Similar to results from analysis of whole kidney hypertrophy, glomerular hypertrophy was attenuated in β−/− diabetic mice (Fig. 6A and B).

Bottom Line: The absence of β produced a significant decrease in total calcineurin activity in the inner medulla (IM) and reduced nuclear factor of activated T-cells (NFATc) activity.In conclusion, loss of the β isoform of calcineurin is sufficient to reproduce beneficial aspects of cyclosporine on diabetic renal hypertrophy but not matrix expansion.Therefore, while multiple signals appear to regulate matrix, calcineurin β appears to be a central mechanism involved in organ hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine/Division of Nephrology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Show MeSH
Related in: MedlinePlus