 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, June 6, 2007, 27(23):6163-6173; doi:10.1523/JNEUROSCI.1306-07.2007
Previous Article | Next Article
Cellular/Molecular
A Role for Transcriptional Repressor Methyl-CpG-Binding Protein 2 and Plasticity-Related Gene Serum- and Glucocorticoid-Inducible Kinase 1 in the Induction of Inflammatory Pain States
Sandrine M. Géranton, Cruz Morenilla-Palao, andStephen P. Hunt Department of Anatomy and Developmental Biology and London Pain Consortium, UCL, London WC1E 6BT, United Kingdom
Correspondence should be addressed to Sandrine M. Géranton, Department of Anatomy and Developmental Biology, UCL, Medawar Building, London WC1E 6BT, UK. Email: ucgasmg{at}ucl.ac.uk
Activity-dependent changes in neurons of the rat superficial dorsal horn are crucial for the induction and maintenance of neuropathic and inflammatory pain states. To identify the molecular mechanisms underlying this sensitization of superficial dorsal horn neurons, we undertook a genome-wide microarray profiling of dorsal horn gene transcripts at various times after induction of peripheral inflammation of the rat ankle joint. At early time points, upregulation of gene expression dominated, but by 7 d, downregulation was predominant. Two to 24 h after inflammation, we identified a small number of highly upregulated transcripts previously shown to be repressed by the Methyl-CpG-binding protein 2 (MeCP2), including serum- and glucocorticoid-inducible kinase (SGK1) and FK 506 binding protein 5, genes known to be important in experience-dependent plasticity. A decrease in expression of SIN3A, a corepressor in the MeCP2 silencing complex, was also found after inflammation. Phosphorylation of MeCP2 regulates activity-dependent gene transcription, and crucially we found that MeCP2 was phosphorylated in lamina I projection neurons 1 h after induction of peripheral inflammation. Lamina I projection neurons have been shown to be essential for the development of most pain states. SGK1 protein was also localized, in part, to lamina I projection neurons, and its expression in the superficial dorsal horn increased after inflammation. Furthermore, antisense knock-down of SGK1 delayed the onset of inflammatory hyperalgesia by 24 h at least. Our results uncover an unexpected complexity in the regulation of gene expression, including the modulation of transcriptional repression, that accompanies development and maintenance of an inflammatory pain state.
Key words: inflammation; lamina I; SGK1; MeCP2; transcriptional repression; antisense technology
Received Feb. 5, 2007; revised April 24, 2007; accepted April 30, 2007.
Correspondence should be addressed to Sandrine M. Géranton, Department of Anatomy and Developmental Biology, UCL, Medawar Building, London WC1E 6BT, UK. Email: ucgasmg{at}ucl.ac.uk
This article has been cited by other articles:
S. M. Geranton, L. Jimenez-Diaz, C. Torsney, K. K. Tochiki, S. A. Stuart, J. L. Leith, B. M. Lumb, and S. P. Hunt
A Rapamycin-Sensitive Signaling Pathway Is Essential for the Full Expression of Persistent Pain States
J. Neurosci., November 25, 2009; 29(47): 15017 - 15027.
[Abstract] [Full Text] [PDF]
L. A. Tebar, S. M. Geranton, C. Parsons-Perez, A. S. Fisher, R. Bayne, A. J. H. Smith, M. Turmaine, S. Perez-Luz, A. Sheasby, C. De Felipe, et al.
Deletion of the mouse RegIII{beta} (Reg2) gene disrupts ciliary neurotrophic factor signaling and delays myelination of mouse cranial motor neurons
PNAS, August 12, 2008; 105(32): 11400 - 11405.
[Abstract] [Full Text] [PDF]
M. F. Arteaga, T. Coric, C. Straub, and C. M. Canessa
A brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons
PNAS, March 18, 2008; 105(11): 4459 - 4464.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|