2. Academic Validation
  3. Galanin regulates M1/M2 polarization of microglia after spinal cord injury through TRPV1/Ca2+/CaMKII/NRF2 signaling pathway

Galanin regulates M1/M2 polarization of microglia after spinal cord injury through TRPV1/Ca2+/CaMKII/NRF2 signaling pathway

  • Int Immunopharmacol. 2025 Aug 13:164:115330. doi: 10.1016/j.intimp.2025.115330.
Zhongwei Zhu 1,  Wenjie Lu 1,  Yaoping Fang 1,  Junyu Zhuang 1,  Jiahui Song 1,  Minghao Jiang 1,  Xiong Cai 1,  Min Chen 1,  Yibo Ying 2,  Yifan Zhang 3,  Aimin Wu 3,  Ao Fang 4,  Sipin Zhu 5,  Zhouguang Wang 6
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 32500, China; National Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 2 National Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
  • 3 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 32500, China.
  • 4 National Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: bxfangao@163.com.
  • 5 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 32500, China. Electronic address: sipinzhu@163.com.
  • 6 The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; National Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: wzhouguang@gmail.com.
PMID: 40811950 DOI: 10.1016/j.intimp.2025.115330
Abstract

Medicine strategies focused on reducing secondary injury and delaying spinal cord injury (SCI) progression by targeting M1 microglial polarization remain uncommon. Galanin (GAL), a neuroendocrine peptide, is encoded by the GAL gene. In this study, we demonstrated that administration of recombinant human GAL peptides in a mouse model of SCI significantly elevated transient receptor potential vanilloid type 1 (TRPV1) receptor expression at the injury site through GALR2, substantially alleviating inflammation during the early stages post-injury. Nuclear factor erythroid 2-related factor 2 (NRF2) is a nuclear transcription factor responsible for activating genes that protect against oxidative stress and toxicity, thereby preserving redox equilibrium. Our results indicated that GAL modulates the CA2+/CaMKII/NRF2 signaling pathway through TRPV1, thereby suppressing the polarization of microglia towards the pro-inflammatory M1 phenotype. This modulation contributes to an improved spinal cord microenvironment and exerts neuroprotective effects following SCI. These findings underscore the therapeutic potential of GAL as an early intervention for inflammation associated with SCI.

Keywords

Galanin; Inflammation; Microglia polarization; Neuroprotection; Spinal cord injury.

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