Regulation of smooth muscle development
Altered contractile protein expression and increased smooth muscle cell proliferation are characteristics of many vascular and pulmonary diseases. The long-term goal of research in my laboratory is to unravel the mechanisms regulating smooth muscle development and differentiation. To begin to accomplish this goal, the molecular mechanisms regulating smooth muscle-specific expression of telokin, a small myosin binding protein, are being elucidated. It is likely that tissue-specific nuclear proteins bind to cis-acting elements in the telokin promoter to regulate telokin transcription in smooth muscle. As telokin is expressed at high levels in visceral as compared to vascular smooth muscle it is likely that there are either different levels of nuclear regulatory proteins or unique nuclear proteins in each of these smooth muscle tissues. The cis-acting elements in the telokin promoter that regulate expression in smooth muscle tissues are being identified in cultured cells and in transgenic mice. Several factors that bind to important regulatory elements have been identified and cloned. The tissue and developmental pattern of expression of these proteins is being analyzed and their role in regulating the expression of telokin and other smooth muscle genes investigated. These studies will help unravel the complex network of interactions that ultimately results in smooth muscle differentiation and provide reagents that can be used to design smooth muscle-specific gene delivery systems. A second area of research being investigated in the laboratory is aimed at understanding the roles of specific myosin light chain kinase (MLCK) isoforms in regulating smooth muscle patho-physiology. Unraveling the roles of MLCK isoforms in regulating smooth muscle contractility, motility and cell division is crucial to our understanding of many different vascular and pulmonary diseases, such as atherosclerosis, hypertension, restenosis following angioplasty, asthma and chronic obstructive pulmonary disease that are associated with alterations in smooth muscle physiology.
