RALY participates in nerve trauma-induced nociceptive hypersensitivity through triggering Eif4g2 gene expression in primary sensory neurons
© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society..
BACKGROUND AND PURPOSE: Peripheral nerve trauma-induced dysregulation of pain-associated genes in the primary sensory neurons of dorsal root ganglion (DRG) contributes to neuropathic pain genesis. RNA-binding proteins participate in gene transcription. We hypothesized that RALY, an RNA-binding protein, participated in nerve trauma-induced dysregulation of DRG pain-associated genes and nociceptive hypersensitivity.
METHODS AND RESULTS: Immunohistochemistry staining showed that RALY was expressed exclusively in the nuclei of DRG neurons. Peripheral nerve trauma caused by chronic constriction injury (CCI) of unilateral sciatic nerve produced time-dependent increases in the levels of Raly mRNA and RALY protein in injured DRG. Blocking this increase through DRG microinjection of adeno-associated virus 5 (AAV5)-expressing Raly shRNA reduced the CCI-induced elevation in the amount of eukaryotic initiation factor 4 gamma 2 (Eif4g2) mRNA and Eif4g2 protein in injured DRG and mitigated the development and maintenance of CCI-induced nociceptive hypersensitivity, without altering basal (acute) response to noxious stimuli and locomotor activity. Mimicking DRG increased RALY through DRG microinjection of AAV5 expressing Raly mRNA up-regulated the expression of Eif4g2 mRNA and Eif4g2 protein in the DRG and led to hypersensitive responses to noxious stimuli in the absence of nerve trauma. Mechanistically, CCI promoted the binding of RALY to the promoter of Eif4g2 gene and triggered its transcriptional activity.
CONCLUSION AND IMPLICATIONS: Our findings indicate that RALY participates in nerve trauma-induced nociceptive hypersensitivity likely through transcriptionally triggering Eif4g2 expression in the DRG. RALY may be a potential target in neuropathic pain management.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:181 |
|---|---|
| Enthalten in: |
British journal of pharmacology - 181(2024), 5 vom: 28. März, Seite 735-751 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Huang, Lina [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 07.02.2024 Date Revised 06.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/bph.16259 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM362780749 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM362780749 | ||
| 003 | DE-627 | ||
| 005 | 20240307232017.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/bph.16259 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1319.xml |
| 035 | |a (DE-627)NLM362780749 | ||
| 035 | |a (NLM)37782223 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Huang, Lina |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a RALY participates in nerve trauma-induced nociceptive hypersensitivity through triggering Eif4g2 gene expression in primary sensory neurons |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.02.2024 | ||
| 500 | |a Date Revised 06.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. | ||
| 520 | |a BACKGROUND AND PURPOSE: Peripheral nerve trauma-induced dysregulation of pain-associated genes in the primary sensory neurons of dorsal root ganglion (DRG) contributes to neuropathic pain genesis. RNA-binding proteins participate in gene transcription. We hypothesized that RALY, an RNA-binding protein, participated in nerve trauma-induced dysregulation of DRG pain-associated genes and nociceptive hypersensitivity | ||
| 520 | |a METHODS AND RESULTS: Immunohistochemistry staining showed that RALY was expressed exclusively in the nuclei of DRG neurons. Peripheral nerve trauma caused by chronic constriction injury (CCI) of unilateral sciatic nerve produced time-dependent increases in the levels of Raly mRNA and RALY protein in injured DRG. Blocking this increase through DRG microinjection of adeno-associated virus 5 (AAV5)-expressing Raly shRNA reduced the CCI-induced elevation in the amount of eukaryotic initiation factor 4 gamma 2 (Eif4g2) mRNA and Eif4g2 protein in injured DRG and mitigated the development and maintenance of CCI-induced nociceptive hypersensitivity, without altering basal (acute) response to noxious stimuli and locomotor activity. Mimicking DRG increased RALY through DRG microinjection of AAV5 expressing Raly mRNA up-regulated the expression of Eif4g2 mRNA and Eif4g2 protein in the DRG and led to hypersensitive responses to noxious stimuli in the absence of nerve trauma. Mechanistically, CCI promoted the binding of RALY to the promoter of Eif4g2 gene and triggered its transcriptional activity | ||
| 520 | |a CONCLUSION AND IMPLICATIONS: Our findings indicate that RALY participates in nerve trauma-induced nociceptive hypersensitivity likely through transcriptionally triggering Eif4g2 expression in the DRG. RALY may be a potential target in neuropathic pain management | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Eif4g2 | |
| 650 | 4 | |a RALY | |
| 650 | 4 | |a dorsal root ganglion | |
| 650 | 4 | |a nerve trauma | |
| 650 | 4 | |a neuropathic pain | |
| 650 | 7 | |a Heterogeneous-Nuclear Ribonucleoprotein Group C |2 NLM | |
| 650 | 7 | |a RALY protein, human |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Sharma, Dilip |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Xiaozhou |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Zhiqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Shaogen |e verfasserin |4 aut | |
| 700 | 1 | |a Munoz, Daisy |e verfasserin |4 aut | |
| 700 | 1 | |a Bekker, Alex |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Huijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Yuan-Xiang |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t British journal of pharmacology |d 1968 |g 181(2024), 5 vom: 28. März, Seite 735-751 |w (DE-627)NLM000001325 |x 1476-5381 |7 nnns |
| 773 | 1 | 8 | |g volume:181 |g year:2024 |g number:5 |g day:28 |g month:03 |g pages:735-751 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/bph.16259 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 181 |j 2024 |e 5 |b 28 |c 03 |h 735-751 | ||