HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 98/6/2344    most recent 01093.2004v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (23) Citing Articles via Google Scholar Google Scholar Articles by Zhou, D. Articles by Chaqour, B. Search for Related Content PubMed PubMed Citation Articles by Zhou, D. Articles by Chaqour, B.

HIGHLIGHTED TOPICS
Biomechanics and Mechanotransduction in Cells and Tissues

Cyr61 mediates the expression of VEGF, _v-integrin, and -actin genes through cytoskeletally based mechanotransduction mechanisms in bladder smooth muscle cells

¹Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia; ²Department of Dermatology, Thomas Jefferson University, Philadelphia, Pennsylvania; and ³Department of Anatomy and Cell Biology, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York

Submitted 30 September 2004 ; accepted in final form 12 January 2005

Application of cyclic strain to bladder smooth muscle (SM) cells results in profound alterations of the histomorphometry, phenotype, and function of the cells. The onset of this process is characterized by the activation of a cascade of signaling events coupled to progressive and, perhaps, interdependent changes of gene expression. In particular, externally applied cyclic stretch to cultured bladder SM cells results in the transient expression of the Cyr61 gene that encodes a cysteine-rich heparin-binding protein originally described as a proangiogenic factor capable of altering the gene programs for angiogenesis, adhesion, and extracellular matrix synthesis. In this study, we investigated the effects of mechanical stretch-induced Cyr61 on the expression of potential mechanosensitive Cyr61 target genes and the signaling pathways involved. We showed that suppression of Cyr61 expression with an adenoviral vector encoding an antisense oligonucleotide reduced mechanical strain-induced VEGF, _v-integrin, and SM -actin gene expression but had no effect on the myosin heavy chain isoforms SM-1 and SM-2. Signaling pathways involving RhoA GTPase, phosphatidyl inositol 3-kinase, and cytoskeletal actin dynamics altered stretch-induced Cyr61 and Cyr61 target genes. Reciprocally, adenovirus-mediated overexpression of Cyr61 in cells cultured under static conditions increased the expression of VEGF, _v-integrin, and SM -actin, as well as that of SM-1 and SM-2 isoforms, suggesting that the effects of a sustained expression of Cyr61 extend to SM specific contractile function. These effects were dependent on integrity of the actin cytoskeleton. Together, these results indicate that Cyr61 is an important determinant of the genetic reprogramming that occurs in mechanically challenged cells.

mechanical stretch; Cyr61; signal transduction; actin cytoskeleton

This article has been cited by other articles:

				J.-J. You, C.-H. Yang, M.-S. Chen, and C.-M. Yang Cysteine-rich 61, a Member of the CCN Family, as a Factor Involved in the Pathogenesis of Proliferative Diabetic Retinopathy Invest. Ophthalmol. Vis. Sci., July 1, 2009; 50(7): 3447 - 3455. [Abstract] [Full Text] [PDF]

				W. A. Kues, S. Sudheer, D. Herrmann, J. W. Carnwath, V. Havlicek, U. Besenfelder, H. Lehrach, J. Adjaye, and H. Niemann Genome-wide expression profiling reveals distinct clusters of transcriptional regulation during bovine preimplantation development in vivo PNAS, December 16, 2008; 105(50): 19768 - 19773. [Abstract] [Full Text] [PDF]

				R. Yang, J. Amir, H. Liu, and B. Chaqour Mechanical strain activates a program of genes functionally involved in paracrine signaling of angiogenesis Physiol Genomics, December 12, 2008; 36(1): 1 - 14. [Abstract] [Full Text] [PDF]

				C. T. Walsh, J. Radeff-Huang, R. Matteo, A. Hsiao, S. Subramaniam, D. Stupack, and J. H. Brown Thrombin receptor and RhoA mediate cell proliferation through integrins and cysteine-rich protein 61 FASEB J, November 1, 2008; 22(11): 4011 - 4021. [Abstract] [Full Text] [PDF]

				J. F. Hardisty, D. C. Anderson, S. Brodie, J. M. Cline, F. F. Hahn, H. Kolenda-Roberts, S. M. Lele, and L. J. Lowenstine Histopathology of the Urinary Bladders of Cynomolgus Monkeys Treated with PPAR Agonists Toxicol Pathol, October 1, 2008; 36(6): 769 - 776. [Abstract] [Full Text] [PDF]

				C. T. Walsh, D. Stupack, and J. H. Brown G Protein-Coupled Receptors Go Extracellular: RhoA Integrates the Integrins Mol. Interv., August 1, 2008; 8(4): 165 - 173. [Abstract] [Full Text] [PDF]

				F. Peng, D. Wu, B. Gao, A. J. Ingram, B. Zhang, K. Chorneyko, R. McKenzie, and J. C. Krepinsky RhoA/Rho-Kinase Contribute to the Pathogenesis of Diabetic Renal Disease Diabetes, June 1, 2008; 57(6): 1683 - 1692. [Abstract] [Full Text] [PDF]

				H. Liu, R. Yang, B. Tinner, A. Choudhry, N. Schutze, and B. Chaqour Cysteine-Rich Protein 61 and Connective Tissue Growth Factor Induce Deadhesion and Anoikis of Retinal Pericytes Endocrinology, April 1, 2008; 149(4): 1666 - 1677. [Abstract] [Full Text] [PDF]

				R. Kivela, H. Kyrolainen, H. Selanne, P. V. Komi, H. Kainulainen, and V. Vihko A single bout of exercise with high mechanical loading induces the expression of Cyr61/CCN1 and CTGF/CCN2 in human skeletal muscle J Appl Physiol, October 1, 2007; 103(4): 1395 - 1401. [Abstract] [Full Text] [PDF]

				A. N. Athanasopoulos, D. Schneider, T. Keiper, V. Alt, U. R. Pendurthi, U. M. Liegibel, U. Sommer, P. P. Nawroth, C. Kasperk, and T. Chavakis Vascular Endothelial Growth Factor (VEGF)-induced Up-regulation of CCN1 in Osteoblasts Mediates Proangiogenic Activities in Endothelial Cells and Promotes Fracture Healing J. Biol. Chem., September 14, 2007; 282(37): 26746 - 26753. [Abstract] [Full Text] [PDF]

				E. J. Kuiper, J. M. Hughes, R. J. Van Geest, I. M. C. Vogels, R. Goldschmeding, C. J. F. Van Noorden, R. O. Schlingemann, and I. Klaassen Effect of VEGF-A on Expression of Profibrotic Growth Factor and Extracellular Matrix Genes in the Retina Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4267 - 4276. [Abstract] [Full Text] [PDF]

				K. Grote, G. Salguero, M. Ballmaier, M. Dangers, H. Drexler, and B. Schieffer The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration Blood, August 1, 2007; 110(3): 877 - 885. [Abstract] [Full Text] [PDF]

				S. Gery, D. Xie, D. Yin, H. Gabra, C. Miller, H. Wang, D. Scott, W. S. Yi, M. L. Popoviciu, J. W. Said, et al. Ovarian Carcinomas: CCN Genes Are Aberrantly Expressed and CCN1 Promotes Proliferation of these Cells Clin. Cancer Res., October 15, 2005; 11(20): 7243 - 7254. [Abstract] [Full Text] [PDF]

				S. M. Cohen Effects of PPAR{gamma} and Combined Agonists on the Urinary Tract of Rats and Other Species Toxicol. Sci., October 1, 2005; 87(2): 322 - 327. [Full Text] [PDF]