Blog
About

  • Record: found
  • Abstract: found
  • Article: not found

Platelet derived growth factor induced tenascin-C transcription is phosphoinositide 3-kinase/Akt-dependent and mediated by Ets family transcription factors.

Journal of Cellular Physiology

drug effects, Base Sequence, Up-Regulation, genetics, Transcription Factors, metabolism, Tenascin, Signal Transduction, Response Elements, RNA, Messenger, chemistry, Proto-Oncogene Proteins c-ets, Promoter Regions, Genetic, pharmacology, Platelet-Derived Growth Factor, physiology, Phosphatidylinositol 3-Kinases, Mutation, Molecular Sequence Data, Models, Biological, Humans, Fibroblasts, Female, cytology, Dermis

Read this article at

ScienceOpenPublisherPubMed
Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      Previous studies have identified several cytokines as inducers of tenascin-C (TN-C) expression in various tissue culture systems. However, the signaling pathways of the regulation of TN-C expression are almost unknown. In this study, we clarified the molecular mechanism(s) underlying the regulation of the TN-C gene by platelet derived growth factor (PDGF) in cultured human dermal fibroblasts. PDGF induced the expression of TN-C protein as well as mRNA in a dose-dependent manner. Actinomycin D, an RNA synthesis inhibitor, significantly blocked the PDGF-mediated upregulation of TN-C mRNA expression, whereas cycloheximide, a protein synthesis inhibitor, did not. The PDGF-mediated induction of TN-C expression was inhibited by the treatment of fibroblasts with a selective phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, or LY294002. These results suggest that PDGF induced the expression of TN-C at a transcriptional level via phosphoinositide3-kinase/Akt signaling pathways. We performed serial 5' deletions and a transient transfection analysis to define the region in the TN-C promoter mediating the responsiveness to PDGF. Overexpression of Sp1, Ets1, or Ets2 activated the TN-C promoter and superinduced TN-C promoter activity stimulated by PDGF, whereas overexpression of Fli1 inhibited the effects of PDGF on TN-C expression. Mutation of the Sp1/3 binding sites or Ets binding sites in the TN-C promoter region responsible to PDGF abrogated the PDGF-inducible promoter activity. Immunoprecipitation analysis revealed that Sp1, Ets1, and Ets2 form a transcriptionally active complex. On the other hand, the interaction of Fli1 with Sp1 decreased after PDGF treatment. These results suggest that the upregulation of TN-C expression by PDGF involves Ets family transcription factors, co-operating with Sp1. Copyright 2005 Wiley-Liss, Inc.

      Related collections

      Author and article information

      Journal
      10.1002/jcp.20527
      16245312

      Comments

      Comment on this article