In:
Journal of Cellular Physiology, Wiley, Vol. 206, No. 3 ( 2006-03), p. 718-727
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. J.Cell.Physiol. © 2005 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0021-9541
,
1097-4652
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
1478143-8
SSG:
12
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