![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1-Adrenergic Receptor Signaling Pathways: Secreted Factors and Interactions with the Extracellular Matrix
Departments of Molecular Cardiology (T.S., R.P., E.P., R.J.G., E.F.P., D.M.P.) and Pathobiology (C.A.d.l.M.), the Lerner Research Institute, the Cleveland Clinic Foundation, Cleveland, Ohio; and Department of Computer Science, University of Akron, Akron, Ohio (Z.-H.D.)
1-Adrenergic receptor (1-ARs) subtypes (1A, 1B, and 1D) regulate multiple signal pathways, such as phospholipase C, protein kinase C (PKC), and mitogen-activated protein kinases. We employed oligonucleotide microarray technology to explore the effects of both short- (1 h) and long-term (18 h) activation of the 1A-AR to enable RNA changes to occur downstream of earlier well characterized signaling pathways, promoting novel couplings. Polymerase chain reaction (PCR) studies confirmed that PKC was a critical regulator of 1A-AR-mediated gene expression, and secreted interleukin (IL)-6 also contributed to gene expression alterations. We next focused on two novel signaling pathways that might be mediated through 1A-AR stimulation because of the clustering of gene expression changes for cell adhesion/motility (syndecan-4 and tenascin-C) and hyaluronan (HA) signaling. We confirmed that 1-ARs induced adhesion in three cell types to vitronectin, an interaction that was also integrin-, FGF7-, and PKC-dependent. 1-AR activation also inhibited cell migration, which was integrin- and PKC-independent but still required secretion of FGF7. 1-AR activation also increased the expression and deposition of HA, a glycosaminoglycan, which displayed two distinct structures: pericellular coats and long cable structures, as well as increasing expression of the HA receptor, CD44. Long cable structures of HA can bind leukocytes, which this suggests that 1-ARs may be involved in proinflammatory responses. Our results indicate 1-ARs induce the secretion of factors that interact with the extracellular matrix to regulate cell adhesion, motility and proinflammatory responses through novel signaling pathways.
Address correspondence to: Dianne M. Perez, Department of Molecular Cardiology NB50, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail: perezd{at}ccf.org
This article has been cited by other articles:
|
|
 |
|
  D. M. Perez, R. S. Papay, and T. Shi {alpha}1-Adrenergic Receptor Stimulates Interleukin-6 Expression and Secretion through Both mRNA Stability and Transcriptional Regulation: Involvement of p38 Mitogen-Activated Protein Kinase and Nuclear Factor-{kappa}B Mol. Pharmacol., July 1, 2009; 76(1): 144 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Lauer, C. Fulop, D. Mukhopadhyay, S. Comhair, S. C. Erzurum, and V. C. Hascall Airway Smooth Muscle Cells Synthesize Hyaluronan Cable Structures Independent of Inter-{alpha}-inhibitor Heavy Chain Attachment J. Biol. Chem., February 20, 2009; 284(8): 5313 - 5323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Lauer, S. C. Erzurum, D. Mukhopadhyay, A. Vasanji, J. Drazba, A. Wang, C. Fulop, and V. C. Hascall Differentiated Murine Airway Epithelial Cells Synthesize a Leukocyte-adhesive Hyaluronan Matrix in Response to Endoplasmic Reticulum Stress J. Biol. Chem., September 19, 2008; 283(38): 26283 - 26296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Lynch and J. G. Ryall Role of {beta}-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease Physiol Rev, April 1, 2008; 88(2): 729 - 767. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
