title: Induction of high mobility group I architectural transcription factors in proliferating vascular smooth muscle in vivo and in vitro.
abstract: Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of arteriosclerosis. Architectural transcription factors of the high mobility group (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 expression in proliferating VSMCs. HMG-I(Y) and HMGI-C mRNAs were barely detectable by Northern analysis in samples prepared from uninjured rat carotid arteries. In contrast, these mRNAs were induced dramatically in carotid arteries 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 developing neointima, and immunocytochemical analysis showed that HMG-I(Y) protein was expressed in the nuclei of these cells. To confirm this association 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 primary 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 proliferating RASMCs in vivo and in vitro. This demonstration suggests that the HMG-I proteins may play an important role in smooth muscle cell proliferation.
authors.affiliation: Cardiovascular Biology Laboratory, Harvard School of Public Health, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Chin
authors.forename: A
authors.initials: A
authors.lastname: Pellacani
authors.forename: C M
authors.initials: CM
authors.lastname: Hsieh
authors.forename: S S
authors.initials: SS
authors.lastname: Lin
authors.forename: M K
authors.initials: MK
authors.lastname: Jain
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: G S
authors.initials: GS
authors.lastname: Huggins
authors.forename: R
authors.initials: R
authors.lastname: Reeves
authors.forename: M A
authors.initials: MA
authors.lastname: Perrella
authors.forename: M E
authors.initials: ME
authors.lastname: Lee
mesh_terms: D000818:Animals; D002404:Catheterization; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D025741:HMGA1a Protein; D006609:High Mobility Group Proteins / Q000096:biosynthesis*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D006609:High Mobility Group Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025741:HMGA1a Protein