NFATc is required for TGFβ-mediated transcriptional regulation of fibronectin

• Type of Material: Article
• Authors: Scott L. Cobbs, Emory University; Jennifer Gooch, Emory University
• Language: English
• Date: 2007-10-19
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2007 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbrc.2007.07.186
• Title of Journal or Parent Work: Biochemical and Biophysical Research Communications
• ISSN: 0006-291X
• Volume: 362
• Issue: 2
• Start Page: 288
• End Page: 294
• Grant/Funding Information: Funding for this work was provided by the NIH/NIDDK DK066422 (JLG).
• Keywords: NFATc1; extracelluar matrix; mesangial cells; TGFβ; calcineurin
• Research Categories: Chemistry, Biochemistry; Biology, General

Abstract

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 TGFβ-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 TGFβ 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 TGFβ-mediated activation of the fibronectin promoter. Finally, stable expression of a dominant negative NFATc protein reduced transcriptional activation of the promoter and inhibited TGFβ-mediated fibronectin expression. In conclusion, TGFß 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.