1. Academic Validation
  2. Bioinformatics and validation reveal spinal cord cathepsin S potential degradation of perineuronal nets in neuropathic pain

Bioinformatics and validation reveal spinal cord cathepsin S potential degradation of perineuronal nets in neuropathic pain

  • Neuropharmacology. 2025 Jun 24:278:110577. doi: 10.1016/j.neuropharm.2025.110577.
Jiahui Pang 1 Ziwei Hu 2 Yubai Zhao 3 Xinli Liu 4 Bo Wang 5 Qian Fang 4 Yin Xu 4 Yingxuan Hu 4 Hui Zeng 4 Wen Wu 6
Affiliations

Affiliations

  • 1 Center of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China; School of Rehabilitation Sciences, Southern Medical University, Guangzhou, China; GuangDong Engineering Technology Research Center of Brain Function Assessment and Neuroregulation Rehabilitation, Guangzhou, China; Institute of Exercise and Rehabilitation Science, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Center of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address: huziwei57@163.com.
  • 3 Center of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Department of Clinical and Rehabilitation Medicine, Guiyang Healthcare Vocational University, Guiyang, China.
  • 4 Center of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  • 5 Center of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Department of Rehabilitation, Wuhan No.1 Hospital, Wuhan, Hubei, China.
  • 6 Center of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China; School of Rehabilitation Sciences, Southern Medical University, Guangzhou, China; GuangDong Engineering Technology Research Center of Brain Function Assessment and Neuroregulation Rehabilitation, Guangzhou, China; Institute of Exercise and Rehabilitation Science, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address: wuwen66@163.com.
Abstract

Neuropathic pain (NP), resulting from nerve damage or diseases, significantly impacts patients' quality of life. Bioinformatics analysis can assist researchers in identifying key molecular pathways involved disease progression. This study aims to investigate the hub genes in the spinal cord of NP rats, with a particular focus on the relationship between Cathepsin S (CTSS) and perineuronal nets (PNNs). Bioinformatics analysis identified Ctss as a hub gene in NP dataset GSE18803. After injury, CTSS expression was significantly upregulated in the spinal cord of NP rats, and the immunofluorescence staining confirmed the degradation of PNNs in the ipsilateral spinal cord lamina V of NP rats. Furthermore, in vitro experiment demonstrated that CTSS promoted the degradation of PNNs. Finally, knockdown CTSS expression spinal cord relived pain and PNNs degradation in NP rats. These findings suggest that CTSS is upregulated in the spinal cord of NP rats and reveal CTSS potential degradation of PNNs.

Keywords

Bioinformatics; CTSS; Neuropathic pain; Perineuronal nets.

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