Research article summary (published 5 May 2004):

Structurally different RGTAs modulate collagen-type expression by cultured aortic smooth muscle cells via different pathways involving fibroblast growth factor-2 or transforming growth factor-beta1.

Full Abstract

We have engineered polymers called ReGeneraTing Agents (RGTAs), which mimic the protecting and potentiating properties of heparan sulfates toward heparin-binding growth factors (HBGF). RGTAs have been shown to optimize cell growth and regulate collagen production in vitro. Here, we studied relationships between RGTA structure and collagen-type expression in aortic smooth muscle cells by using two RGTAs, the carboxylmethylsulfate dextran RG-1503 and the carboxylmethylsulfate dextran with added benzylamide RG-1192. RG-1192 specifically induced a fivefold decrease in collagen III synthesis. This effect was abolished by FGF-2 neutralizing antibody. RG-1192 and FGF-2 acted synergistically to decrease collagen III. RG-1192 was more effective than heparin in this process. RG-1192 increased the pericellular localization of FGF-2 and protected FGF-2 from proteolysis. Surface plasmon resonance analysis indicated a Kd of 15.7 nM for the RG-1192/FGF-2 interaction (10.6 nM for the heparin/FGF-2 interaction). The structurally different RG-1503 (without benzylamide) did not interact with FGF-2 and worked synergistically with TGF-beta1 to specifically induce a twofold increase in collagen V. RGTAs with different structures exert different modulating effects on the collagen phenotype. Selection of appropriate RGTAs, which had been shown to enhance in vivo tissue repair, may provide a mean of correcting collagen abnormalities in vascular disorders and more generally in fibrotic diseases.

Author information

Author/s: Alexakis, Catherine (C); Mestries, Patricia (P); Garcia, Stéphanie (S); Petit, Emmanuel (E); Barbier, Véronique (V); Papy-Garcia, Dulce (D); Sagot, Marie-Astride (MA); Barritault, Denis (D); Caruelle, Jean Pierre (JP); Kern, Patrick (P);

Affiliation: CRRET/CNRS FRE 2412, Faculté des Sciences, Université de Paris 12, Créteil Cedex, France.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J), published in United States. (Language: eng)

Reference: 2004-Jul; vol 18 (issue 10) : pp 1147-9

Dates: Created 2004/06/30; Completed 2005/01/05; Revised 2006/11/15;

PMID: 15132978, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: 18 Feb 2009 00:00:00)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Aorta - cytology Cells, Cultured - drug effects; metabolism Collagen Type I - biosynthesis; genetics Collagen Type III - biosynthesis; genetics Collagen Type V - biosynthesis; genetics Dextrans - chemistry; pharmacology Drug Evaluation, Preclinical Drug Synergism Fibroblast Growth Factor 2 - physiology

Gene Expression Regulation - drug effects Heparin - pharmacology Muscle, Smooth, Vascular - cytology Myocytes, Smooth Muscle - drug effects; metabolism Oligosaccharides - chemistry; pharmacology Structure-Activity Relationship Surface Plasmon Resonance Sus scrofa Transforming Growth Factor beta - physiology Transforming Growth Factor beta1

Associated Chemicals: Collagen Type I (0) ; Collagen Type III (0) ; Collagen Type V (0) ; Oligosaccharides (0) ; RG 1503 (0) ; RG1192 (0) ; Transforming Growth Factor beta (0) ; Transforming Growth Factor beta1 (0) ; Fibroblast Growth Factor 2 (103107-01-3) ; Dextrans (9004-54-0) ; Heparin (9005-49-6)

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