TGF-beta1 generates a specific multicomponent extracellular matrix in human coronary SMC.
BACKGROUND
Transforming growth factor (TGF-beta(1)) is postulated to play an important role in maintaining the structure and function of arterial tissue and protection against development of arteriosclerosis. The TGF-beta(1)-induced production of a stable extra-cellular matrix-rich plaque phenotype is suggested to be part of the protection against a switch to an unstable rupture-prone arteriosclerotic plaque.


METHODS
This study addresses the question of whether the expression profile and the type of extra-cellular matrix (ECM) generated by TGF-beta(1) stimulation have the structural feature of a fibril-rich stable matrix. Seventeen genes codings for ECM components of human coronary smooth muscle cells (SMCs) after a 24-h stimulation by TGF-beta(1) have been analyzed.


RESULTS
Real-time RT-PCR was used to quantify the mRNA of genes under investigation. It was found that after TGF-beta(1) stimulation (a) the up-regulation of COL1A1-specific mRNA was associated with increased [(3)H]proline incorporation into the alpha-1 and -2 chains of collagen type I, (b) the up-regulation of biglycan- and syndecan-1-specific mRNA corresponded to an increased [(35)S]sulphate and [4,5-(3)H]leucine incorporation into the biglycan molecule and to an increase of syndecan-1 protein, (c) the up-regulated FGF-2 gene accounted predominantly for the ECM-bound subfraction of FGF-2-protein and (d) fibronectin and thrombospondin exhibited a significantly higher mRNA level. In contrast collagen XIV, a minor collagen type, and the proteoglycan decorin were down-regulated. The down-regulated decorin changed its structure by elongation and reduced GlcA to IdoA epimerization of the dermatan sulphate side-chain as judged by [(35)S]sulphate metabolic labelling experiments. No significant changes in response to TGF-beta(1) were observed for the collagen types III, VI and XVI, for versican, perlecan and the syndecans-2 and -4.


CONCLUSIONS
It was concluded from the data that the TGF-beta(1)-induced formation of a highly specific multicomponent extra-cellular matrix on coronary arterial SMCs could provide in vivo mechanical strength to the neointima in arteriosclerotic lesions and to the fibrous cap overlying the lipid core.
Schmidt
A
A
Leibniz-Institute of Arteriosclerosis Research, University of Muenster, Domagkstrasse 3, D-48149 Muenster, Germany. annschm@uni-muenster.de
Lorkowski
S
S
Seidler
D
D
Breithardt
G
G
Buddecke
E
E
D058578:Biglycan; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D058575:Decorin; D015536:Down-Regulation / Q000235:genetics; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D024022:Fibrillar Collagens / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D053668:Syndecan-1; D053667:Syndecans; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000235:genetics
C546884:BGN protein, human; D058578:Biglycan; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D024022:Fibrillar Collagens; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2