2. Academic Validation
  3. CtBP1-LSD1 complex drives ErbB2 activation via H3K9me2 demethylation in DRGs during paclitaxel-induced neuropathic pain

CtBP1-LSD1 complex drives ErbB2 activation via H3K9me2 demethylation in DRGs during paclitaxel-induced neuropathic pain

  • Cell Biol Toxicol. 2025 Dec 18;42(1):1. doi: 10.1007/s10565-025-10122-7.
Hsien-Yu Peng # 1 2,  Cheng-Yuan Lai 2,  Gin-Den Chen # 3,  Yun-Chih Peng 4,  Chou-Ming Yeh 5 6,  Tzer-Bin Lin 7 8 9,  Hsueh-Hsiao Wang 1,  Jen-Kun Cheng 1 10,  Po-Sheng Yang 1 11,  Chia-Man Chou 12 13,  Dylan Chou 1,  Kuan-Hung Lin 2 14 15,  Siao-Tong Nie 2,  Ming-Chun Hsieh 16
Affiliations

Affiliations

  • 1 School of Medicine, College of Medicine, MacKay Medical University, No.46, Sec. 3, Zhongzheng Rd, Sanzhi Dist, New Taipei, 25245, Taiwan.
  • 2 Institute of Biomedical Sciences, College of Medicine, MacKay Medical University, New Taipei, Taiwan.
  • 3 Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taichung, Taiwan.
  • 4 MacKay Memorial Hospital, Taipei, Taiwan.
  • 5 Division of Thoracic Surgery, Asia University Hospital, Taichung, Taiwan.
  • 6 Central Taiwan University of Science and Technology, Taichung, Taiwan.
  • 7 Institute of Translational Medicine and New Drug Development, College of Medicine, China Medical University, Taichung, Taiwan.
  • 8 Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 9 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
  • 10 Department of Anesthesiology, MacKay Memorial Hospital, Taipei, Taiwan.
  • 11 Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
  • 12 Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
  • 13 Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
  • 14 Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
  • 15 Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 16 School of Medicine, College of Medicine, MacKay Medical University, No.46, Sec. 3, Zhongzheng Rd, Sanzhi Dist, New Taipei, 25245, Taiwan. [email protected].
  • # Contributed equally.
PMID: 41410814 DOI: 10.1007/s10565-025-10122-7
Abstract

Paclitaxel (PTX), a commonly utilized chemotherapy drug, is linked to peripheral neuropathy, which limits dosing and significantly affects patients' quality of life. C-terminal binding protein 1 (CtBP1) is a transcriptional coregulator that participates in epigenetic gene regulation, but its role in PTX-induced neuropathic pain remains unclear. In this study, the role of CtBP1 in PTX-induced neuropathic pain is examined, with a focus on its epigenetic regulation in the dorsal root ganglia (DRGs). PTX administration markedly increased CtBP1 protein levels in DRG neurons, which coincided with the development and continuation of mechanical allodynia and thermal hyperalgesia in rat models. Our findings also revealed that CtBP1 interacts with the Histone Demethylase LSD1-a regulator of H3K9me2-at ErbB2 promoter sites in DRG neurons. PTX treatment increased CtBP1 protein levels, which subsequently induced LSD1 expression and decreased H3K9me2 protein levels at the ErbB2 promoter, indicating epigenetic activation of ErbB2 signaling in DRG neurons implicated in neuropathic pain. Reducing either CtBP1 or LSD1 expression reversed ErbB2 upregulation and attenuated PTX-induced pain sensitivity. These results suggest that the CtBP1-LSD1 complex epigenetically increases ErbB2 expression in DRG neurons, contributing to PTX-induced neuropathy. Targeting the CtBP1-LSD1 pathway could represent a promising therapeutic strategy for the treatment of chemotherapy-induced neuropathic pain.

Keywords

CtBP1; DRG; ErbB2; LSD1; Neuropathic pain; Paclitaxel.

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