Document Detail

Ultraviolet irradiation induces Smad7 via induction of transcription factor AP-1 in human skin fibroblasts.
MedLine Citation:
PMID:  15579469     Owner:  NLM     Status:  MEDLINE    
Smad7 functions as an endogenous negative regulator of transforming growth factor-beta (TGF-beta)/SMAD signaling. The TGF-beta/SMAD pathway is a major regulator of collagen production in connective tissue. Reduced expression of SMAD7 has been reported in TGF-beta-mediated fibrotic diseases, characterized by overproduction of collagen. Solar ultraviolet (UV) irradiation reduces collagen production by fibroblasts in human skin in vivo. We have investigated regulation of Smad7 gene expression by UV irradiation in human skin fibroblasts. UV irradiation transiently increased SMAD7 mRNA and protein levels. Induction of SMAD7 mRNA and protein was maximal within 5 h and returned to initial basal levels 24 h post-UV irradiation. UV irradiation induced Smad7 promoter-reporter activity 3-fold. The Smad7 promoter contains functional enhancer sequences that bind transcription factors SMAD3 and activator protein-1 (AP-1). UV irradiation reduced protein binding to the Smad3 enhancer and increased binding to the AP-1 enhancer. Deletion of the AP-1 binding site in the Smad7 promoter completely abolished UV stimulation of SMAD7 transcription. Deletion of the Smad3 element had no effect on UV irradiation-induced promoter activity. UV irradiation increased mRNA and protein expression of the AP-1 family members, c-Jun and c-Fos, which bound to the AP-1 element in the Smad7 promoter. Furthermore, overexpression of dominant negative c-Jun substantially reduced UV irradiation induction of SMAD7 transcription. These data demonstrate that induction of Smad7 gene expression by UV irradiation is mediated via induction of the transcription factor AP-1 in human skin fibroblasts.
Taihao Quan; Tianyuan He; John J Voorhees; Gary J Fisher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-12-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-28     Completed Date:  2005-04-07     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8079-85     Citation Subset:  IM    
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MeSH Terms
Base Sequence
Binding Sites
Blotting, Northern
Blotting, Western
Cells, Cultured
Collagen / metabolism
DNA-Binding Proteins / metabolism*
Fibroblasts / metabolism*
Gene Deletion
Gene Expression Regulation
Genes, Dominant
Genes, Reporter
JNK Mitogen-Activated Protein Kinases / metabolism
Luciferases / metabolism
Molecular Sequence Data
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Proteins c-fos / metabolism
RNA / chemistry
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Skin / metabolism*
Smad7 Protein
Time Factors
Trans-Activators / metabolism*
Transcription Factor AP-1 / metabolism*
Transforming Growth Factor beta / metabolism
Ultraviolet Rays
Grant Support
AG19364-02/AG/NIA NIH HHS; R01 AG019364/AG/NIA NIH HHS; R01 AG019364-05/AG/NIA NIH HHS
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Proto-Oncogene Proteins c-fos; 0/RNA, Messenger; 0/SMAD7 protein, human; 0/Smad7 Protein; 0/Trans-Activators; 0/Transcription Factor AP-1; 0/Transforming Growth Factor beta; 63231-63-0/RNA; 9007-34-5/Collagen; EC 1.13.12.-/Luciferases; EC Mitogen-Activated Protein Kinases

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