IRT-1, a novel interferon-gamma-responsive transcript encoding a growth-suppressing basic leucine zipper protein

Interferon-gamma (IFN-gamma) inhibits proliferation of vascular smooth muscle cells (VSMCs) in culture and reduces arterial restenosis post-balloon angioplasty. The identification and characterization of IFN-gamma-specific transcripts in VSMCs are an important approach to discern the molecular mechanisms underlying vascular proliferative disease. In this report, we describe IRT-1, a novel mRNA transcript constitutively expressed in a number of human tissues, but expressed in human VSMCs only when they are stimulated with IFN-gamma. This mRNA expression is induced >200-fold 72 h after IFN-gamma treatment. IRT-1 mRNA is also acutely expressed in rat carotid arteries that are injured by balloon angioplasty. The IRT-1 cDNA transcript encodes a basic protein that contains a leucine zipper motif, a core nuclear localization sequence, and a single strongly hydrophobic region. Constitutive IRT-1 mRNA expression in human peripheral blood lymphocytes is reduced when these cells are stimulated to proliferate. Overexpression of IRT-1 protein in VSMCs alters their morphology and dramatically reduces their proliferative capacity. This study suggests that IRT-1 is an IFN-gamma-inducible factor that may regulate the progression of vascular proliferative diseases.