CWC22-Mediated Alternative Splicing of Spp1 Regulates Nociception in Inflammatory Pain.
Neuroscience
; 535: 50-62, 2023 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-37838283
ABSTRACT
Increasing evidence suggests that alternative splicing plays a critical role in pain, but its underlying mechanism remains elusive. Herein, we employed complete Freund's adjuvant (CFA) to induce inflammatory pain in mice. A combination of genomics research techniques, lentivirus-based genetic manipulations, behavioral tests, and molecular biological technologies confirmed that splicing factor Cwc22 mRNA and CWC22 protein were elevated in the spinal dorsal horn at 3 days after CFA injection. Knockdown of spinal CWC22 by lentivirus transfection (lenti-shCwc22) reversed CFA-induced thermal hyperalgesia and mechanical allodynia, whereas upregulation of spinal CWC22 (lenti-Cwc22) in naïve mice precipitated pain. Comprehensive transcriptome and genome analysis identified the secreted phosphoprotein 1 (Spp1) as a potential gene of CWC22-mediated alternative splicing, however, only Spp1 splicing variant 4 (Spp1 V4) was involved in thermal and mechanical nociceptive regulation. In conclusion, our findings demonstrate that spinal CWC22 regulates Spp1 V4 to participate in CFA-induced inflammatory pain. Blocking CWC22 or CWC22-mediated alternative splicing may provide a novel therapeutic target for the treatment of persistent inflammatory pain.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Empalme Alternativo
/
Nocicepción
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2023
Tipo del documento:
Article
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
/
EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA