Elevated plasma phosphate levels are signifcantly associated with progression of chronic kidneydisease (CKD). Interstitial fibrosis is an important factor in the progression of CKD. In this studywe investigate the role of inorganic phosphate in stimulating fibronectin (FN) synthesis in akidney fibroblast cell line (NRK-49F). We find that phosphate increases FN abundance andmessage in a dose–dependent fashion and that both ERK1/2 and AKT are important signalingpathways that mediate phosphate-dependent FN expression in NRK-49F cells. Moreoverphosphate srimulates the expression of the transcription factors osterix and NFATc1, whichform complexes and mediate FN synthesis. Another transcription factor involved in phosphatedependentFN synthesis is the AP1 family member c-Fos. In summary we show that evenmildly elevated serum phosphate levels can induce synthesis of the interstitial matrix proteinfibronectin through activation of ERK1/2 and AKT signaling pathways in kidney fibroblasts andthat the synthesis of fibronectin is mediated by a transcriptional complex consisting of NFATc1,osterix and c-Fos.

Keywords:
Fibroblast, Akt, Osterix, Fibronectin, NFATc1, c-fos
This content is only available via PDF.
© 2012 S. Karger AG, Basel
2012
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.