Induction of the transcriptional repressor Yin Yang-1 by vascular cell injury - Autocrine/paracrine role of endogenous fibroblast growth factor-2

Yin Yang-1 (YY1) is a multifunctional transcription factor that can repress the expression of many growth factor, hormone, and cytokine genes implicat ed in atherogenesis. YY1 expression is activated in rat vascular smooth mus cle cells shortly after injury. YY1 DNA binding activity paralleled elevate d protein levels in the nucleus. Smooth muscle cell injury triggered the ra pid extracellular release of immunoreactive fibroblast growth factor-2 (FGF -2). YY1 induction after injury was blocked by neutralizing antibodies dire cted against FGF-2. This growth factor increased YY1 mRNA and protein expre ssion and stimulated YY1 binding and transcriptional activity. Overexpressi on of YY1 inhibited smooth muscle cell replication. immunohistochemical ana lysis demonstrated YY1 staining in medial smooth muscle cells, coincident w ith FGF-2 expression. Proliferating cell nuclear antigen staining, in contr ast, was confined mainly to the atherosclerotic intima. This is the first d emonstration that YY1 is induced by either injury or FGF-2, is differential ly expressed in normal and diseased human arteries, and that its overexpres sion inhibits vascular smooth muscle but not endothelial cell replication.