This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 89/2/131    most recent hh1401.093582v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jones, F. S. Articles by Jones, P. L. Search for Related Content PubMed PubMed Citation Articles by Jones, F. S. Articles by Jones, P. L. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Pulmonary Hypertension Related Collections Remodeling ACE/Angiotension receptors Animal models of human disease Gene expression Acute myocardial infarction

(Circulation Research. 2001;89:131.)
© 2001 American Heart Association, Inc.

Molecular Medicine

Prx1 Controls Vascular Smooth Muscle Cell Proliferation and Tenascin-C Expression and Is Upregulated With Prx2 in Pulmonary Vascular Disease

Frederick S. Jones, Robyn Meech, David B. Edelman, Rebecca J. Oakey, Peter Lloyd Jones

From the Department of Neurobiology (F.R.J., R.M.), Scripps Research Institute, La Jolla, and The Neurosciences Institute (D.B.E.), San Diego, Calif; Children’s Hospital of Philadelphia and Department of Pediatrics (R.J.O., P.L.J.), University of Pennsylvania School of Medicine, Philadelphia, Penn; and Department of Pediatrics (P.L.J.), Section of Critical Care, University of Colorado Health Sciences Center, Denver, Colo.

Correspondence to Peter Lloyd Jones, PhD, University of Colorado Health Sciences Center, 4200 East Ninth Ave, B-131, Denver, CO 80242. E-mail peter.jones{at}uchsc.edu

Abstract— Prx1 and Prx2 are homeobox transcription factors expressed during vasculogenesis. To begin to elucidate how Prx1 and Prx2 are regulated and function in the adult vasculature, in situ hybridization studies were performed. Prx1 and Prx2 mRNAs 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. Because catabolism of the extracellular matrix (ECM) is a critical step in the development of vascular disease, we investigated whether changes in vascular smooth muscle cell (SMC)–ECM interactions regulate Prx1 and Prx2. A10 SMCs cultured on native type I collagen showed low levels of Prx1 and Prx2 mRNA expression, whereas cells cultured on denatured collagen showed higher levels of expression of both genes. At a functional level, transfection of SMCs with a Prx1 expression plasmid significantly increased their growth. Because TN-C also promotes SMC growth and its expression is also upregulated by denatured collagen, we tested and thereafter showed that Prx1 expression significantly enhances TN-C gene promoter activity 20-fold. Similar experiments conducted with truncated Prx1 proteins showed that the N-terminal portion and the homeodomain of Prx1 were necessary to induce the bulk of TN-C promoter 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.

Key Words: tenascin-C • homeobox genes • pulmonary

This article has been cited by other articles:

				P. L. Jones Move On!: Smooth Muscle Cell Motility Paired Down Circ. Res., March 30, 2007; 100(6): 757 - 760. [Full Text] [PDF]

				L. Jin, M. J. Kern, C. A. Otey, B. R. Wamhoff, and A. V. Somlyo Angiotensin II, Focal Adhesion Kinase, and PRX1 Enhance Smooth Muscle Expression of Lipoma Preferred Partner and its Newly Identified Binding Partner Palladin to Promote Cell Migration Circ. Res., March 30, 2007; 100(6): 817 - 825. [Abstract] [Full Text] [PDF]

				R. Chapados, K. Abe, K. Ihida-Stansbury, D. McKean, A. T. Gates, M. Kern, S. Merklinger, J. Elliott, A. Plant, H. Shimokawa, et al. ROCK Controls Matrix Synthesis in Vascular Smooth Muscle Cells: Coupling Vasoconstriction to Vascular Remodeling Circ. Res., October 13, 2006; 99(8): 837 - 844. [Abstract] [Full Text] [PDF]

				K. Ihida-Stansbury, D. M. McKean, K. B. Lane, J. E. Loyd, L. A. Wheeler, N. W. Morrell, and P. L. Jones Tenascin-C is induced by mutated BMP type II receptors in familial forms of pulmonary arterial hypertension Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L694 - L702. [Abstract] [Full Text] [PDF]

				K. R. Stenmark, N. Davie, M. Frid, E. Gerasimovskaya, and M. Das Role of the Adventitia in Pulmonary Vascular Remodeling Physiology, April 1, 2006; 21(2): 134 - 145. [Abstract] [Full Text] [PDF]

				M. Rabinovitch Cellular and Molecular Pathobiology of Pulmonary Hypertension Conference Summary Chest, December 1, 2005; 128(6_suppl): 642S - 646S. [Full Text] [PDF]

				M. Rabinovitch Cellular and Molecular Pathobiology of Pulmonary Hypertension Conference Summary Chest, December 1, 2005; 128(6_suppl): 642S - 646S. [Full Text] [PDF]

				K. G. Norsett, A. Laegreid, M. Langaas, S. Worlund, R. Fossmark, H. L. Waldum, and A. K. Sandvik Molecular characterization of rat gastric mucosal response to potent acid inhibition Physiol Genomics, June 16, 2005; 22(1): 24 - 32. [Abstract] [Full Text] [PDF]

				R. W. Dettman and R. H. Steinhorn Connecting the Cells: Vascular Differentiation via Homeobox Genes and Extracellular Matrix in the Distal Lung Circ. Res., June 11, 2004; 94(11): 1406 - 1407. [Full Text] [PDF]

				K. Ihida-Stansbury, D. M. McKean, S. A. Gebb, J. F. Martin, T. Stevens, R. Nemenoff, A. Akeson, J. Vaughn, and P. L. Jones Paired-Related Homeobox Gene Prx1 Is Required for Pulmonary Vascular Development Circ. Res., June 11, 2004; 94(11): 1507 - 1514. [Abstract] [Full Text] [PDF]

				T. A. Stevens, J. S. Iacovoni, D. B. Edelman, and R. Meech Identification of Novel Binding Elements and Gene Targets for the Homeodomain Protein BARX2 J. Biol. Chem., April 9, 2004; 279(15): 14520 - 14530. [Abstract] [Full Text] [PDF]

				D. M. McKean, L. Sisbarro, D. Ilic, N. Kaplan-Alburquerque, R. Nemenoff, M. Weiser-Evans, M. J. Kern, and P. L. Jones FAK induces expression of Prx1 to promote tenascin-C-dependent fibroblast migration J. Cell Biol., April 28, 2003; 161(2): 393 - 402. [Abstract] [Full Text] [PDF]