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Regulation of Vascular Smooth Muscle Cell Growth and Adhesion by Paired-Related Homeobox Genes* FREE TO VIEW

Frederick S. Jones; David M. McKean; Robyn Meech; David B. Edelman; Rebecca J. Oakey; Peter Lloyd Jones, PhD
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*From Department of Neurobiology (Mssrs. F. Jones and Edelman, and Ms. Meech), The Scripps Research Institute, La Jolla, CA; the Department of Pediatrics (Ms. Oakey and Dr. P. Jones), The University of Pennsylvania School of Medicine, Philadelphia, PA; and the Department of Pediatrics (Mr. McKean), The University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Peter L. Jones, PhD, Department of Pediatrics, University of Colorado Health Sciences Center, 4200 E 9th Ave, Denver, CO 80262

Chest. 2002;121(3_suppl):89S-90S. doi:10.1378/chest.121.3_suppl.89S
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Prx1 and Prx2 genes encode homeobox transcription factors that are expressed during vasculogenesis. To determine how Prx genes are regulated and function in the adult vasculature, in situ hybridization studies were performed. Prx1 and Prx2 messenger RNAs were not detected in normal adult rat pulmonary arteries; however, both genes were induced with vascular disease, colocalizing to sites of tenascin-C (TN-C) expression. Since the degradation of the extracellular matrix is critical for the development of vascular disease, we investigated whether changes in vascular smooth muscle cell (SMC)-extracellular matrix interactions regulate Prx1 and Prx2. A10 SMCs cultured on native type-I collagen showed low levels of Prx1 and Prx2 messenger RNA expression, whereas cells cultured on denatured collagen showed higher levels of expression of both genes. At a functional level, the transfection of SMCs with a Prx1 expression plasmid significantly increased their growth. Since TN-C also promotes SMC growth, and since its expression also is up-regulated by denatured collagen, we tested and thereafter showed that Prx1 binds to the TN-C gene promoter and significantly enhances its activity. These findings support the hypothesis that Prx genes are regulated by changes in SMC adhesion and play key morphoregulatory roles during the development and progression of pulmonary vascular disease in adults.

Abbreviations: SMC = smooth muscle cell; TN-C = tenascin-C




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