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Protease-activated receptor 4 activation increases the expression of calcitonin gene-related peptide mRNA and protein in dorsal root ganglion neurons.
J Neurosci Res. 2013 Dec; 91(12):1551-62.JN

Abstract

Accumulating evidence demonstrates that nociceptor activation evokes a rapid change in mRNA and protein levels of calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG) neurons. Although the colocalization of CGRP and protease-activated receptor-4 (PAR4), a potent modulator of pain processing and inflammation, was detected in DRG neurons, the role of PAR4 activation in the expression of CGRP has not been investigated. In the present study, the expression of CGRP and activation (phosphorylation) of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in rat DRG neurons were measured by immunofluorescence, real-time PCR, and Western blotting after AYPGKF-NH2 (selective PAR4-activating peptide; PAR4-AP) intraplantar injection or treatment of cultured DRG neurons. The expression of CGRP in cultured DRG neurons was also assessed after treatment with AYPGKF-NH2 with preaddition of PD98059 (an inhibitor for ERK1/2 pathway). Results showed that PAR4-AP intraplantar injection or treatment of cultured DRG neurons evoked significant increases in DRG cells displaying CGRP immunoreactivity and cytoplasmic and nuclear staining for phospho-ERK1/2 (p-ERK1/2). Percentages of total DRG neurons expressing both CGRP and PAR4 or p-ERK1/2 also increased significantly at 2 hr after PAR4-AP treatment. Real-time PCR and Western blotting showed that PAR4-AP treatment significantly increased expression of CGRP mRNA and protein levels in DRG neurons. The PAR4 activation-evoked CGRP expression both at mRNA and at protein levels was significantly inhibited after p-ERK1/2 was inhibited by PD98059. These results provide evidence that activation of PAR4 upregulates the expression of CGRP mRNA and protein levels in DRG neurons via the p-ERK1/2 signal pathway.

Authors+Show Affiliations

Department of Anatomy, Taishan Medical University, Shandong Province, Taian, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24105611

Citation

Wang, Zhaojin, et al. "Protease-activated Receptor 4 Activation Increases the Expression of Calcitonin Gene-related Peptide mRNA and Protein in Dorsal Root Ganglion Neurons." Journal of Neuroscience Research, vol. 91, no. 12, 2013, pp. 1551-62.
Wang Z, Chen D, Zhang Z, et al. Protease-activated receptor 4 activation increases the expression of calcitonin gene-related peptide mRNA and protein in dorsal root ganglion neurons. J Neurosci Res. 2013;91(12):1551-62.
Wang, Z., Chen, D., Zhang, Z., Zhang, R., An, S., & Yu, L. (2013). Protease-activated receptor 4 activation increases the expression of calcitonin gene-related peptide mRNA and protein in dorsal root ganglion neurons. Journal of Neuroscience Research, 91(12), 1551-62. https://doi.org/10.1002/jnr.23280
Wang Z, et al. Protease-activated Receptor 4 Activation Increases the Expression of Calcitonin Gene-related Peptide mRNA and Protein in Dorsal Root Ganglion Neurons. J Neurosci Res. 2013;91(12):1551-62. PubMed PMID: 24105611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protease-activated receptor 4 activation increases the expression of calcitonin gene-related peptide mRNA and protein in dorsal root ganglion neurons. AU - Wang,Zhaojin, AU - Chen,Dan, AU - Zhang,Zaifeng, AU - Zhang,Rui, AU - An,Shuhong, AU - Yu,Lianfeng, Y1 - 2013/09/16/ PY - 2012/12/14/received PY - 2013/06/26/revised PY - 2013/06/27/accepted PY - 2013/10/10/entrez PY - 2013/10/10/pubmed PY - 2014/6/18/medline KW - DRG KW - calcitonin gene-related peptide KW - immunofluorescence KW - p-ERK1/2 KW - protease-activated receptor-4 SP - 1551 EP - 62 JF - Journal of neuroscience research JO - J Neurosci Res VL - 91 IS - 12 N2 - Accumulating evidence demonstrates that nociceptor activation evokes a rapid change in mRNA and protein levels of calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG) neurons. Although the colocalization of CGRP and protease-activated receptor-4 (PAR4), a potent modulator of pain processing and inflammation, was detected in DRG neurons, the role of PAR4 activation in the expression of CGRP has not been investigated. In the present study, the expression of CGRP and activation (phosphorylation) of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in rat DRG neurons were measured by immunofluorescence, real-time PCR, and Western blotting after AYPGKF-NH2 (selective PAR4-activating peptide; PAR4-AP) intraplantar injection or treatment of cultured DRG neurons. The expression of CGRP in cultured DRG neurons was also assessed after treatment with AYPGKF-NH2 with preaddition of PD98059 (an inhibitor for ERK1/2 pathway). Results showed that PAR4-AP intraplantar injection or treatment of cultured DRG neurons evoked significant increases in DRG cells displaying CGRP immunoreactivity and cytoplasmic and nuclear staining for phospho-ERK1/2 (p-ERK1/2). Percentages of total DRG neurons expressing both CGRP and PAR4 or p-ERK1/2 also increased significantly at 2 hr after PAR4-AP treatment. Real-time PCR and Western blotting showed that PAR4-AP treatment significantly increased expression of CGRP mRNA and protein levels in DRG neurons. The PAR4 activation-evoked CGRP expression both at mRNA and at protein levels was significantly inhibited after p-ERK1/2 was inhibited by PD98059. These results provide evidence that activation of PAR4 upregulates the expression of CGRP mRNA and protein levels in DRG neurons via the p-ERK1/2 signal pathway. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/24105611/Protease_activated_receptor_4_activation_increases_the_expression_of_calcitonin_gene_related_peptide_mRNA_and_protein_in_dorsal_root_ganglion_neurons_ L2 - https://doi.org/10.1002/jnr.23280 DB - PRIME DP - Unbound Medicine ER -