Document Detail

Human collagen Krox up-regulates type I collagen expression in normal and scleroderma fibroblasts through interaction with Sp1 and Sp3 transcription factors.
MedLine Citation:
PMID:  17698844     Owner:  NLM     Status:  MEDLINE    
Despite several investigations, the transcriptional mechanisms that regulate the expression of both type I collagen genes (COL1A1 and COL1A2) in either physiological or pathological situations, such as scleroderma, are not completely known. We have investigated the role of hc-Krox transcription factor on type I collagen expression by human dermal fibroblasts. hc-Krox exerted a stimulating effect on type I collagen protein synthesis and enhanced the corresponding mRNA steady-state levels of COL1A1 and COL1A2 in foreskin fibroblasts (FF), adult normal fibroblasts (ANF), and scleroderma fibroblasts (SF). Forced hc-Krox expression was found to up-regulate COL1A1 transcription through a -112/-61-bp sequence in FF, ANF, and SF. Knockdown of hc-Krox by short interfering RNA and decoy strategies confirmed the transactivating effect of hc-Krox and decreased substantially COL1A1 transcription levels in all fibro-blast types. The -112/-61-bp sequence bound specifically hc-Krox but also Sp1 and CBF. Attempts to elucidate the potential interactions between hc-Krox, Sp1, and Sp3 revealed that all of them co-immunoprecipitate from FF cellular extracts when a c-Krox antibody was used and bind to the COL1A1 promoter in chromatin immunoprecipitation assays. Moreover, hc-Krox DNA binding activity to its COL1A1-responsive element is increased in SF, cells producing higher amounts of type I collagen compared with ANF and FF. These data suggest that the regulation of COL1A1 gene transcription in human dermal fibroblasts involves a complex machinery that implicates at least three transcription proteins, hc-Krox, Sp1, and Sp3, which could act in concert to up-regulate COL1A1 transcriptional activity and provide evidence for a pro-fibrotic role of hc-Krox.
Magdalini Kypriotou; Gallic Beauchef; Christos Chadjichristos; Russell Widom; Emmanuelle Renard; Sergio A Jimenez; Joseph Korn; François-Xavier Maquart; Thierry Oddos; Otto Von Stetten; Jean-Pierre Pujol; Philippe Galéra
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Publication Detail:
Type:  Journal Article     Date:  2007-08-13
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  282     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-29     Completed Date:  2007-12-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32000-14     Citation Subset:  IM    
Laboratoire de Biochimie du Tissu Conjonctif, Université de Caen/Basse-Normandie, IFR ICORE 146, FacultédeMédecine, CHU Niveau 3, Avenue de la Côte de Nacre, 14032 Caen Cedex, France.
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MeSH Terms
Base Sequence
Collagen Type I / genetics*
DNA-Binding Proteins / genetics,  metabolism*
Fibroblasts / metabolism*
Foreskin / cytology,  metabolism
Molecular Sequence Data
RNA Interference
RNA, Small Interfering
Scleroderma, Systemic
Skin / cytology,  metabolism
Sp1 Transcription Factor / metabolism*
Sp3 Transcription Factor / metabolism*
Transcription Factors / genetics,  metabolism*
Transcription, Genetic
Reg. No./Substance:
0/Collagen Type I; 0/DNA-Binding Proteins; 0/RNA, Small Interfering; 0/Sp1 Transcription Factor; 0/Transcription Factors; 0/ZBTB7B protein, human; 148710-94-5/Sp3 Transcription Factor

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