Induction of high mobility group I architectural transcription factors in proliferating vascular smooth muscle in vivo and in vitro

Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of arte riosclerosis. Architectural transcription factors of the high mobility grou p (HMG)-I family have been implicated in the control of cell proliferation and gene expression. We studied the pattern of HMG-I mRNA and protein expre ssion in proliferating VSMCs. HMG-I(Y) and HMGI-C mRNAs were barely detecta ble by Northern analysis in samples prepared from uninjured rat carotid art eries. In contrast, these mRNAs were induced dramatically in carotid arteri es 2 and 5-6 days after balloon injury. By in situ hybridization at 6 days after injury, the induced mRNAs localized to smooth muscle cells of the dev eloping neointima, and immunocytochemical analysis showed that HMG-I(Y) pro tein was expressed in the nuclei of these cells. To confirm this associatio n between HMG-I protein induction and cell growth, we assessed HMG-I(Y) and HMGI-C mRNA expression in rat aortic smooth muscle cells (RASMCs) in prima ry culture. The HMG-I mRNAs were barely detectable in quiescent RASMCs but were induced markedly by serum stimulation. This induction of mRNA by serum was time dependent and peaked at 9 h, Western blot analysis confirmed that HMG-I(Y) protein induction also occurred in vitro. To our knowledge, this is the first demonstration of induction of HMG-I protein expression in prol iferating RASMCs in vivo and in vitro. This demonstration suggests that the HMG-I proteins may play an important role in smooth muscle cell proliferat ion. (C) 1999 Academic Press.