Transcription of rat TRPV1 utilizes a dual promoter system that is positively regulated by nerve growth factor
Open Access
- 4 January 2007
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 101 (1), 212-222
- https://doi.org/10.1111/j.1471-4159.2006.04363.x
Abstract
The capsaicin receptor, also known as ‘transient receptor potential vanilloid receptor subtype 1’ (TRPV1, VR1), is an ion channel subunit expressed in primary afferent nociceptors, which plays a critical role in pain transduction and thermal hyperalgesia. Increases in nociceptor TRPV1 mRNA and protein are associated with tissue injury–inflammation. As little is understood about what controls TRPV1 RNA transcription in nociceptors, we functionally characterized the upstream portion of the rat TRPV1 gene. Two functional rTRPV1 promoter regions and their transcription initiation sites were identified. Although both promoter regions directed transcriptional activity in nerve growth factor (NGF) treated rat sensory neurons, the upstream Core promoter was the most active in cultures enriched in sensory neurons. Because NGF is a key modulator of inflammatory pain, we examined the effect of NGF on rTRPV1 transcription in PC12 cells. NGF positively regulated transcriptional activity of both rTRPV1 promoter regions in PC12 cells. We propose that the upstream regulatory region of the rTRPV1 gene is composed of a dual promoter system that is regulated by NGF. These findings support the hypothesis that NGF produced under conditions of tissue injury and/or inflammation directs an increase of TRPV1 expression in nociceptors in part through a transcription-dependent mechanism.Keywords
This publication has 61 references indexed in Scilit:
- Expression of vanilloid VR1 receptor in PC12 cellsNeurochemistry International, 2004
- Bringing the role of mRNA decay in the control of gene expression into focusTrends in Genetics, 2004
- Isolation of an mRNA binding protein homologue that is expressed in nociceptorsEuropean Journal of Neuroscience, 2004
- Signal transduction: Putting translation before transcriptionCancer Cell, 2003
- Diversified transcription initiation complexes expand promoter selectivity and tissue-specific gene expressionGenes & Development, 2003
- Signaling Pathways for PC12 Cell Differentiation: Making the Right ConnectionsScience, 2002
- Nerve Growth Factor Uses Ras/ERK and Phosphatidylinositol 3-Kinase Cascades to Up-regulate theN-Methyl-d-aspartate Receptor 1 PromoterPublished by Elsevier BV ,2001
- The Genomic Organization of the Gene Encoding the Vanilloid Receptor: Evidence for Multiple Splice VariantsGenomics, 2001
- The “initiator” as a transcription control elementCell, 1989
- Neuron‐Enriched cultures of adult rat dorsal root ganglia: Establishment, characterization, survival, and neuropeptide expression in response to trophic factorsJournal of Neuroscience Research, 1987