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TGF‐β 1 generates a specific multicomponent extracellular matrix in human coronary SMC
Author(s) -
Schmidt A.,
Lorkowski S.,
Seidler D.,
Breithardt G.,
Buddecke E.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01658.x
Subject(s) - decorin , biglycan , extracellular matrix , fibulin , fibronectin , transforming growth factor , vitronectin , syndecan 1 , proteoglycan , lumican , microbiology and biotechnology , chemistry , versican , biology , biochemistry , cell
Background Transforming growth factor (TGF‐β 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‐β 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. Materials and methods This study addresses the question of whether the expression profile and the type of extra‐cellular matrix (ECM) generated by TGF‐β 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‐β 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‐β 1 stimulation (a) the up‐regulation of COL1A1‐specific mRNA was associated with increased [ 3 H]proline incorporation into the α‐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‐β 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‐β 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.