Open AccessChondroitin sulphate decreases collagen synthesis in normal and scleroderma fibroblasts through a Smad‐independent TGF‐β pathway – implication of C‐Krox and Sp1
Author(s) -
Renard Emmanuelle,
Chadjichristos Christos,
Kypriotou Magdalini,
Beauchef Gallic,
Bordat Pascal,
Dompmartin Anne,
Widom Russell L.,
Boumediene Karim,
Pujol JeanPierre,
Galéra Philippe
Publication year - 2008
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00287.x
Subject(s) - smad , transforming growth factor , transcription (linguistics) , type i collagen , chemistry , microbiology and biotechnology , procollagen peptidase , gene expression , transcription factor , messenger rna , biology , gene , biochemistry , endocrinology , linguistics , philosophy
Despite several investigations, the transcriptional mechanisms which 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. In this study, we determined the effects of both native ichtyan chondroïtin sulphate (CS) and its derived hydrolytic fragments (CSf) on human normal (NF) and scleroderma (SF) fibroblasts. Here, we demonstrate for the first time that CS and CSf exert an inhibitory effect on type I collagen protein synthesis and decrease the corresponding mRNA steady‐state levels of COL1A1 and COL1A2 in NF and SF. These glycosaminoglycan molecules repress COL1A1 gene transcription through a ‐112/‐61 bp sequence upstream the start site of transcription and imply hc‐Krox and Sp1 transcription factors. In addition, CS and CSf induced a down‐regulation of TβRI expression. As a conclusion, our findings highlight a possible new role for CS and CSf as anti‐fibrotic molecules and could help in elucidating the mechanisms of action by which CS and CSf exert their inhibitory effect on type I collagen synthesis.