| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Histology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
The cysteine-rich protein 61 (Cyr61) is a signaling molecule with functions in cell migration, adhesion, and proliferation. This protein is encoded by an immediate early gene whose expression is mainly induced by serum growth factors. Here we show that Cyr61 mRNA levels increase sharply in response to cyclic mechanical stretch applied to cultured bladder smooth muscle cells. Stretch-induced changes of Cyr61 transcripts were transient and accompanied by an increase of the encoded protein that localized mainly to the cytoplasm and nucleus of the cells. With the use of pharmacological agents that interfere with known signaling pathways, we show that transduction mechanisms involving protein kinase C and phosphatidylinositol 3-kinase activation partly blocked stretch-induced Cyr61 gene expression. Selective inhibition of Rho kinase pathways altered this stretch effect as well. Meanwhile, using inhibitors of the actin cytoskeleton, we show that Cyr61 gene expression is sensitive to mechanisms that sense actin dynamics. These results establish the regulation of Cyr61 gene by mechanical stretch and provide clues to the key signaling molecules involved in this process.
smooth muscle cells; signal transduction
This article has been cited by other articles:
|
|
 |
|
  A. S. Dobroff, H. Wang, V. O. Melnikova, G. J. Villares, M. Zigler, L. Huang, and M. Bar-Eli Silencing cAMP-response Element-binding Protein (CREB) Identifies CYR61 as a Tumor Suppressor Gene in Melanoma J. Biol. Chem., September 18, 2009; 284(38): 26194 - 26206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hanna, H. Liu, J. Amir, Y. Sun, S. W. Morris, M. A. Q. Siddiqui, L. F. Lau, and B. Chaqour Mechanical Regulation of the Proangiogenic Factor CCN1/CYR61 Gene Requires the Combined Activities of MRTF-A and CREB-binding Protein Histone Acetyltransferase J. Biol. Chem., August 21, 2009; 284(34): 23125 - 23136. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
B. Chaqour, R. Yang, and Q. Sha Mechanical Stretch Modulates the Promoter Activity of the Profibrotic Factor CCN2 through Increased Actin Polymerization and NF-{kappa}B Activation J. Biol. Chem., July 21, 2006; 281(29): 20608 - 20622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zhou, D. J. Herrick, J. Rosenbloom, and B. Chaqour Cyr61 mediates the expression of VEGF, {alpha}v-integrin, and {alpha}-actin genes through cytoskeletally based mechanotransduction mechanisms in bladder smooth muscle cells J Appl Physiol, June 1, 2005; 98(6): 2344 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Adam, S. H. Eaton, C. Estrada, A. Nimgaonkar, S.-C. Shih, L. E. H. Smith, I. S. Kohane, D. Bagli, and M. R. Freeman Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells Physiol Genomics, December 15, 2004; 20(1): 36 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Chen, M. J. Hubal, E. P. Hoffman, P. D. Thompson, and P. M. Clarkson Molecular responses of human muscle to eccentric exercise J Appl Physiol, December 1, 2003; 95(6): 2485 - 2494. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Sawai, K. Mori, M. Mukoyama, A. Sugawara, T. Suganami, M. Koshikawa, K. Yahata, H. Makino, T. Nagae, Y. Fujinaga, et al. Angiogenic Protein Cyr61 is Expressed by Podocytes in Anti-Thy-1 Glomerulonephritis J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1154 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Thiruchelvam, P. Nyirady, D. M. Peebles, C. H. Fry, P. M. Cuckow, and A. S. Woolf Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder Am. J. Pathol., April 1, 2003; 162(4): 1271 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Chaqour, C. Whitbeck, J.-S. Han, E. Macarak, P. Horan, P. Chichester, and R. Levin Cyr61 and CTGF are molecular markers of bladder wall remodeling after outlet obstruction Am J Physiol Endocrinol Metab, October 1, 2002; 283(4): E765 - E774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Inoue, K. Matsuda, M. Itoh, H. Kawaguchi, H. Tomoike, T. Aoyagi, R. Nagai, M. Hori, Y. Nakamura, and T. Tanaka Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5 Hum. Mol. Genet., July 15, 2002; 11(15): 1775 - 1784. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
