Document Detail


NFATc is required for TGFbeta-mediated transcriptional regulation of fibronectin.
MedLine Citation:
PMID:  17719012     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Calcineurin is an important regulator of extracellular matrix (ECM) accumulation in the kidney but functions in a cell-specific manner. Previously, we identified a novel role for calcineurin in mesangial cells where calcineurin activity is required for TGFbeta-mediated induction of fibronectin expression. In this study, we examined the role of the calcineurin substrate NFATc in transcriptional regulation of fibronectin. First, inhibition of calcineurin blocks TGFbeta induction of the fibronectin promoter. Moreover, expression of constitutively active calcineurin in mesangial cells is sufficient to increase fibronectin transcription. Next, inhibition of the calcineurin substrate NFATc1 blocked TGFbeta-mediated activation of the fibronectin promoter. Finally, stable expression of a dominant-negative NFATc protein reduced transcriptional activation of the promoter and inhibited TGFbeta-mediated fibronectin expression. In conclusion, TGFbeta activation of calcineurin in mesangial cells results in regulation of ECM accumulation at least in part by direct transcriptional activity of NFATc on the fibronectin promoter.
Authors:
Scott L Cobbs; Jennifer L Gooch
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-08-13
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  362     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-04     Completed Date:  2007-11-19     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  288-94     Citation Subset:  IM    
Affiliation:
Department of Medicine/Division of Nephrology, Emory University School of Medicine, Atlanta, GA 30322, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcineurin / antagonists & inhibitors,  metabolism
Cell Line
Cells, Cultured
Cyclosporine / pharmacology
DNA-Binding Proteins / genetics,  metabolism
Dose-Response Relationship, Drug
Electrophoretic Mobility Shift Assay
Fibronectins / genetics,  metabolism*
Gene Expression Regulation / drug effects
Glomerular Mesangium / cytology,  drug effects,  metabolism
Luciferases / genetics,  metabolism
NFATC Transcription Factors / genetics,  metabolism*
Protein Binding / drug effects
Rats
Recombinant Fusion Proteins / genetics,  metabolism
Tacrolimus / pharmacology
Transcription, Genetic / drug effects
Transfection
Transforming Growth Factor beta / pharmacology*
Grant Support
ID/Acronym/Agency:
DK066422/DK/NIDDK NIH HHS; R01 DK066422-04/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Fibronectins; 0/NFATC Transcription Factors; 0/Recombinant Fusion Proteins; 0/Transforming Growth Factor beta; 109581-93-3/Tacrolimus; 59865-13-3/Cyclosporine; EC 1.13.12.-/Luciferases; EC 3.1.3.16/Calcineurin
Comments/Corrections

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