Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells

• Published in: American Journal of Physiology: Cell Physiology Vol. 292; no. 1; pp. C59 - C69
• Main Authors: Kawai-Kowase, Keiko, Owens, Gary K
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2007
• Subjects: Animals; Cell Differentiation - physiology; Cells; Gene Expression Regulation; Genes; Genetic Markers; Genotype & phenotype; Humans; Muscle, Smooth, Vascular - physiology; Myocytes, Smooth Muscle - physiology; Phenotype; Platelet-Derived Growth Factor - physiology; Proto-Oncogene Proteins c-sis
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00394.2006

1 Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia; and 2 Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan Smooth muscle cell (SMC) differentiation is an essential component of vascular development and these cells perform biosynthetic, proliferative, and contractile roles in the vessel wall. SMCs are not terminally differentiated and possess the ability to modulate their phenotype in response to changing local environmental cues. The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms involved in controlling phenotypic switching of SMC with particular focus on examination of processes that contribute to the repression of SMC marker genes. We discuss the environmental cues which actively regulate SMC phenotypic switching, such as platelet-derived growth factor-BB, as well as several important regulatory mechanisms required for suppressing expression of SMC-specific/selective marker genes in vivo, including those dependent on conserved G/C-repressive elements, and/or highly conserved degenerate CArG elements found in the promoters of many of these marker genes. Finally, we present evidence indicating that SMC phenotypic switching involves multiple active repressor pathways, including Krüppel-like zinc finger type 4, HERP, and ERK-dependent phosphorylation of Elk-1 that act in a complementary fashion. serum response factor; platelet-derived growth factor-BB Address for reprint requests and other correspondence: G. K. Owens, Dept. Molecular Physiology and Biological Physics, Univ. of Virginia, MR5 Rm. 1220, 415 Lane Rd., Charlottesville, VA 22908 (e-mail: gko{at}virginia.edu )