No abstract

No abstract

No abstract

Background: Polyamines are known to play important roles in the proliferation and differentiation of many types of cells. However, in the testis, where polyamines such as spermidine and spermine exist in high concentrations, their roles still remains to be elucidated.

Abstract-Proliferation and ␣ v ␤ 3 integrin-dependent migration of vascular smooth muscle cells are suppressed on polymerized type I collagen. To identify genes specifically regulated in human smooth muscle cells by polymerized collagen, we used the suppressive subtraction hybridization technique. Compared with smooth muscle cells cultured on monomer collagen, polymerized collagen suppresses the following: (1) a number of other extracellular matrix proteins, including fibronectin, thrombospondin-1, tenascin-C, and cysteine-rich protein 61; (2) actin binding proteins including ␣-actinin; (3) signaling molecules; (4) protein synthesis-associated proteins; and (5) genes with unknown functions. Some of the identified genes, including cysteine-rich protein 61, show unique kinetics of mRNA regulation by monomer or polymerized collagen distinct from growth factors, suggesting extracellular matrix-specific gene modulation. Moreover, in vivo balloon catheter-mediated injury to the rat carotid artery induces many of the genes that are suppressed by polymerized collagen. Protein levels of thrombospondin-1 and fibronectin are also suppressed by polymerized collagen. Thrombospondin-1-mediated smooth muscle cell migration on vitronectin is significantly inhibited after culture on polymerized collagen for 24 hours, which is associated with decreased ␣-actinin accumulation at focal adhesions. Thus, polymerized type I collagen dynamically regulates gene expression, pericellular accumulation of extracellular matrix molecules, and the response to a given matrix molecule. Key Words: thrombospondin-1 Ⅲ platelet-derived growth factor Ⅲ ␣-actinin Ⅲ filamin Ⅲ balloon injury M igration of vascular smooth muscle cells (SMCs) from the media into the intima contributes to progression of atherosclerotic lesions and restenosis after balloon angioplasty. 1 SMCs in the normal media are surrounded by extracellular matrix (ECM) molecules, including collagen type I, III, and IV and laminin. SMC interaction with matrix components can significantly influence their ability to respond to growth factors and/or chemoattractants and can promote the modulation of SMCs from a contractile to a synthetic phenotype. 2 Breakdown of the matrix may be necessary for initiation of SMC migration. 3 A majority of cell-cell and cell-matrix interactions are mediated by specific transmembrane adhesion receptors of the integrin family of proteins. 4,5 These molecules assemble as heterodimers through the noncovalent association of ␣ and ␤ subunits. 4,5 Integrins serve as transmembrane links between the ECM and the cell surface, resulting in increased adhesion. Occupancy and clustering of integrins can activate intracellular signaling pathways and induce transcription factors and subsequent gene expression. 4,6 Thus, integrins can influence cell migration not only by the regulation of adhesion and spreading but also by modulation of intracellular signaling events.We have recently demonstrated that SMCs are arrested in G 1 on polymerized type I collagen fibrils in vitro, ...