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Down-regulation of human type II collagen gene expression by transforming growth factor-beta 1 (TGF-beta 1) in articular chondrocytes involves SP3/SP1 ratio.
J Biol Chem. 2002 Nov 15; 277(46):43903-17.JB

Abstract

Although transforming growth factor beta1 (TGF-beta1) is generally considered as a stimulator of type I collagen production in smooth organs, we found that it can inhibit type II collagen biosynthesis in primary rabbit articular chondrocytes (RAC) at transcriptional levels. Constructs of promoter and first intron sequences associated with the luciferase reporter gene were used to delineate the gene sequences involved in TGF-beta1 control of human COL2A1 gene transcription. Cotransfection of these DNA fragments with a TbetaRII/I cDNA hybrid receptor, capable of inducing a TGF-beta1 dominant negative effect, showed that TGF-beta1 inhibits specifically COL2A1 gene transcription in RAC by a 63-bp proximal promoter. Footprint and gel retardation analyses revealed that the TGF-beta1-induced inhibition effect exerted through the 63-bp promoter sequence implies a multimeric complex that binds to the -41/-33 sequence and involves Sp1 and Sp3 transcription factors. Transfection of decoy Sp-binding oligonucleotides corroborated the implication of the proximal promoter in the TGF-beta1-induced inhibition of COL2A1 gene transcription. In addition, TGF-beta1 was found to increase the expression of Sp3 without significant changes to its binding level, but repressed both the biosynthesis and binding activity of Sp1. In functional assays, Sp3 inhibited the 63-bp promoter activity and prevented Sp1 induction of transcription. These findings suggest that TGF-beta1 inhibition of COL2A1 gene transcription in RAC is mediated by an increase of the Sp3/Sp1 ratio and by the repression of Sp1 transactivating effects on that gene.

Authors+Show Affiliations

Laboratoire de Biochimie du Tissu Conjonctif, Faculté de Médecine, CHU niveau 3, Avenue de Côte de Nacre, 14032, Caen Cedex, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12186868

Citation

Chadjichristos, Christos, et al. "Down-regulation of Human Type II Collagen Gene Expression By Transforming Growth Factor-beta 1 (TGF-beta 1) in Articular Chondrocytes Involves SP3/SP1 Ratio." The Journal of Biological Chemistry, vol. 277, no. 46, 2002, pp. 43903-17.
Chadjichristos C, Ghayor C, Herrouin JF, et al. Down-regulation of human type II collagen gene expression by transforming growth factor-beta 1 (TGF-beta 1) in articular chondrocytes involves SP3/SP1 ratio. J Biol Chem. 2002;277(46):43903-17.
Chadjichristos, C., Ghayor, C., Herrouin, J. F., Ala-Kokko, L., Suske, G., Pujol, J. P., & Galéra, P. (2002). Down-regulation of human type II collagen gene expression by transforming growth factor-beta 1 (TGF-beta 1) in articular chondrocytes involves SP3/SP1 ratio. The Journal of Biological Chemistry, 277(46), 43903-17.
Chadjichristos C, et al. Down-regulation of Human Type II Collagen Gene Expression By Transforming Growth Factor-beta 1 (TGF-beta 1) in Articular Chondrocytes Involves SP3/SP1 Ratio. J Biol Chem. 2002 Nov 15;277(46):43903-17. PubMed PMID: 12186868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Down-regulation of human type II collagen gene expression by transforming growth factor-beta 1 (TGF-beta 1) in articular chondrocytes involves SP3/SP1 ratio. AU - Chadjichristos,Christos, AU - Ghayor,Chafik, AU - Herrouin,Jean-Francois, AU - Ala-Kokko,Leena, AU - Suske,Gunthram, AU - Pujol,Jean-Pierre, AU - Galéra,Philippe, Y1 - 2002/08/16/ PY - 2002/8/21/pubmed PY - 2003/1/3/medline PY - 2002/8/21/entrez SP - 43903 EP - 17 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 277 IS - 46 N2 - Although transforming growth factor beta1 (TGF-beta1) is generally considered as a stimulator of type I collagen production in smooth organs, we found that it can inhibit type II collagen biosynthesis in primary rabbit articular chondrocytes (RAC) at transcriptional levels. Constructs of promoter and first intron sequences associated with the luciferase reporter gene were used to delineate the gene sequences involved in TGF-beta1 control of human COL2A1 gene transcription. Cotransfection of these DNA fragments with a TbetaRII/I cDNA hybrid receptor, capable of inducing a TGF-beta1 dominant negative effect, showed that TGF-beta1 inhibits specifically COL2A1 gene transcription in RAC by a 63-bp proximal promoter. Footprint and gel retardation analyses revealed that the TGF-beta1-induced inhibition effect exerted through the 63-bp promoter sequence implies a multimeric complex that binds to the -41/-33 sequence and involves Sp1 and Sp3 transcription factors. Transfection of decoy Sp-binding oligonucleotides corroborated the implication of the proximal promoter in the TGF-beta1-induced inhibition of COL2A1 gene transcription. In addition, TGF-beta1 was found to increase the expression of Sp3 without significant changes to its binding level, but repressed both the biosynthesis and binding activity of Sp1. In functional assays, Sp3 inhibited the 63-bp promoter activity and prevented Sp1 induction of transcription. These findings suggest that TGF-beta1 inhibition of COL2A1 gene transcription in RAC is mediated by an increase of the Sp3/Sp1 ratio and by the repression of Sp1 transactivating effects on that gene. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12186868/Down_regulation_of_human_type_II_collagen_gene_expression_by_transforming_growth_factor_beta_1__TGF_beta_1__in_articular_chondrocytes_involves_SP3/SP1_ratio_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=12186868 DB - PRIME DP - Unbound Medicine ER -