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: M T Chin, A Pellacani, C M Hsieh, S S Lin, M K Jain, A Patel, G S Huggins, R Reeves, M A Perrella, M E Lee
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 31 Issue 12 Pg. 2199-205 (Dec 1999) ISSN: 0022-2828 [Print] England
• PMID: 10640447 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 1999 Academic Press.

Chemical References

• High Mobility Group Proteins
• RNA, Messenger
• Transcription Factors
• HMGA1a Protein

Topics

• Animals
• Catheterization
• Cell Division (physiology)
• Cells, Cultured
• HMGA1a Protein
• High Mobility Group Proteins (biosynthesis)
• Male
• Muscle, Smooth, Vascular (pathology, physiology)
• RNA, Messenger (biosynthesis, genetics)
• Rats
• Rats, Sprague-Dawley
• Transcription Factors (biosynthesis)
• Up-Regulation