Transgenic model of smooth muscle cell cycle reentry: expression pattern of the collageneous matrix.

BACKGROUND: We have previously shown that genetically induced smooth muscle cell (SMC) cycle reentry in transgenic mouse models expressing the SV40 T antigen (TAg) resulted in adaptive arterial remodeling. The present investigation targeted the in vitro expression pattern of the collageneous matrix associated with TAg-induced SMC cycle modulation. METHODS: SMC cultures were established from the transgenic model expressing temperature-sensitive TAg. This allowed inducible transgene expression at the permissive temperature of 33 degrees C compared with the restrictive temperature of 39.5 degrees C. To distinguish a transgene effect from a temperature effect, SMCs with constitutively expressed TAg were used as controls. Data were obtained using array technology, Northern blotting, reverse transcription polymerase chain reaction, and zymography. RESULTS: TAg-induced SMC cycle reentry resulted in significant down-regulation of matrix metalloproteinase (MMP)-3, whereas MMP-2, -9, and -11 were not influenced. In addition, SMC cycle reentry resulted in significantly increased RNA levels of procollagen alpha2(IV), procollagen alpha2(V), and procollagen alpha1(XI), whereas procollagen alpha1(III) and procollagen alpha1(VIII) were down-regulated. Studies of the RNA expression levels of granulocyte-macrophage colony-stimulating factor revealed an up-regulation of this proinflammatory and matrix-modulating cytokine. CONCLUSIONS: This transgenic model provides evidence that TAg-induced cell cycle reentry is associated with a complex modulation of the collageneous matrix. Factors identified in this in vitro study reveal a comprehensive expression pattern of candidates, which might allow the vessel to undergo adaptive arterial remodeling under in vivo conditions. Our results will give rise to further investigations to elaborate on this hypothesis and to improve understanding of the role of such factors in vascular diseases.