Promoter sequences involved in transforming growth factor beta1 gene induction in HaCaT keratinocytes after gamma irradiation.

Details

Serval ID
serval:BIB_D5AC88F4097D
Type
Article: article from journal or magazin.
Collection
Publications
Title
Promoter sequences involved in transforming growth factor beta1 gene induction in HaCaT keratinocytes after gamma irradiation.
Journal
Radiation research
Author(s)
Gault N., Vozenin-Brotons M.C., Calenda A., Lefaix J.L., Martin M.T.
ISSN
0033-7587 (Print)
ISSN-L
0033-7587
Publication state
Published
Issued date
03/2002
Peer-reviewed
Oui
Volume
157
Number
3
Pages
249-255
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Transforming growth factor beta 1 (TGFB1) is a cytokine involved in the development of both acute and late cutaneous radiation syndromes. We previously demonstrated that ionizing radiation induces TGFB1 expression in vivo in pig skin within a few hours. The purpose of the present study was to develop an in vitro human model to identify the mechanisms of this early activation. Accordingly, human HaCaT keratinocytes were irradiated with a single dose of 20 Gy. First, radiation-induced TGFB1 overexpression was checked at both the transcriptional and transductional levels in HaCaT cells. Then electrophoretic mobility shift assays (EMSA) and transient transfection with various TGFB1 promoter constructs were used to identify the sequences involved in regulating this promoter. EMSA analysis showed the induction of nuclear protein binding activity by gamma irradiation to the -365 AP1 sequence (TGTCTCA), suggesting the involvement of AP1 sequences in the regulation of TGFB1 transcription. In gene reporter assays, maximal TGFB1 promoter activation was found for the longest construct, which contains two AP1 sequences. However, assays with constructs including deletions showed that these two AP1 sequences were not sufficient to confer TGFB1 inducibility. These results showed for the first time, to our knowledge, that transcriptional regulation is involved in radiation-induced activation of TGFB1 gene expression.

Keywords
Cell Line, Gamma Rays, Humans, Keratinocytes/metabolism, Keratinocytes/radiation effects, Promoter Regions, Genetic, Protein Binding, Transcription Factors/metabolism, Transcriptional Activation, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta/metabolism
Pubmed
Web of science
Create date
27/04/2018 15:25
Last modification date
20/08/2019 15:55
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