Oude Alink, M. (2012) Transfecting and perfecting: Regulating the “roots” of pain perception :Transcriptional regulation of the nociceptive receptors TRPV1 and P2X3 by Runx1 and C/EBPβ in dorsal root ganglia. thesis, Medicine.
Full text available on request.Abstract
The TRPV1 channel and P2X3 receptor have an important role in acute nociceptive pain, inflammatory pain and neuropathic pain sensation. Studies showed that antagonists for TRPV1 and P2X3 resulted in decreased pain sensation, but resulted in side effects and cause compensatory up-regulation of other nociceptive receptors. The regulation of several nociceptive receptors by a single transcription factor might therefore lead to more efficient pain therapies. In 2006, Chen et al. identified Runx1 as a transcription factor that regulates the expression of several nociceptive receptors, including TRPV1 and P2X3. In the neuron like cell lineage PC12, Ugarte et al. recently identified a transcriptional role of C/EBPβ in the regulation of P2X3 and TRPV1. In this research project we aimed to interfere with the expression of Runx1 and C/EBPβ in rat DRG in vitro, by means of respectively electroporation and lentiviral transduction. By down-regulating these transcription factors, we hypothesised to subsequently decrease the expression of TRPV1 and P2X3. Although the protocol for electroporation was significantly improved during this research project, we have not been able to down-regulate either Runx1 or C/EBPβ. The lentiviral transductions resulted in a non-significant increase of C/EBPβ, probably caused by the inflammatory effect of the lentivirus. More experiments should be performed to achieve successful down-regulation of Runx1 and C/EBPβ in rat DRGs, and give insight in the possibilities to decrease TRPV1 and P2X3 in this manner. To some extent, the knowledge acquired during this research project has paved the path for these, and other experiments using both electroporation and lentiviral transduction in cultured rat DRGs.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Faculty supervisor: and Putten, Prof. Dr. Ir. Michel J.A.M. van |
| Supervisor name: | External supervisor: and Mathijssen van Zundert, Dr. Brigitte and Centro de Investigaciones Biomedicas: and Universidad de Andres Bello, Santiago |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:46 |
| Last Modified: | 25 Jun 2020 10:46 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/774 |
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