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 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.
Chin
M T
MT
Cardiovascular Biology Laboratory, Harvard School of Public Health, Brigham and Women's Hospital, Boston, MA 02115, USA.
Pellacani
A
A
Hsieh
C M
CM
Lin
S S
SS
Jain
M K
MK
Patel
A
A
Huggins
G S
GS
Reeves
R
R
Perrella
M A
MA
Lee
M E
ME
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
D006609:High Mobility Group Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025741:HMGA1a Protein