2. Academic Validation
  3. Deficiency of KIF15 contributes to oxaliplatin-induced cold hypersensitivity by limiting annexin A2 and enhancing TRPA1 localization in DRG neuronal membrane

Deficiency of KIF15 contributes to oxaliplatin-induced cold hypersensitivity by limiting annexin A2 and enhancing TRPA1 localization in DRG neuronal membrane

  • Neuropharmacology. 2025 May 15:269:110343. doi: 10.1016/j.neuropharm.2025.110343.
Liu-Ying Wu 1,  Meng-Nan Zhai 1,  Xue-Qiang Bai 2,  Cheng He 2,  Yun-Ying Guo 2,  Yu-Qi Zhang 2,  Juan Wang 2,  Yong-Tao Gao 3,  Qi-Feng Tu 4,  Mei Liu 5,  Jun-Jie Chen 6,  Zhi-Jun Zhang 1
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu Province, China; Department of Human Anatomy, Medical School of Nantong University, Nantong, 226001, Jiangsu Province, China.
  • 2 Department of Human Anatomy, Medical School of Nantong University, Nantong, 226001, Jiangsu Province, China.
  • 3 Department of Anesthesiology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu Province, China.
  • 4 Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, 226001, Jiangsu Province, China.
  • 5 Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, 226001, Jiangsu Province, China. Electronic address: liumei@ntu.edu.cn.
  • 6 Department of Anesthesiology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu Province, China. Electronic address: junjie97@163.com.
PMID: 39914618 DOI: 10.1016/j.neuropharm.2025.110343
Abstract

Effective treatments for oxaliplatin-induced cold hypersensitivity remain a significant clinical challenge, primarily due to gaps in our understanding of the underlying pathophysiology. Our previous studies have indicated that Kinesin-12 (KIF15) is expressed in neurons, suggesting its potential involvement in neurodevelopment and neuronal plasticity. However, its role in mediating chemotherapy-induced pain in primary sensory neurons has not yet been reported. In this study, we found that KIF15-knockout (Kif15-KO) mice showed an increase in cold sensitivity, with this heightened cold hypersensitivity being dependent on the accumulation of the TRP ankyrin 1 (TRPA1) channel on the cell membrane. We further demonstrated that in a model of oxaliplatin-induced peripheral neuropathy (OIPN), KIF15 expression was markedly reduced, coinciding with an increase in TRPA1 membrane localization and a physical interaction between KIF15 and Annexin A2 in peripheral sensory neurons. This suggests a mechanistic link where the loss of KIF15 disrupts the function of Annexin A2, enhancing the localization of TRPA1 on the cell membrane of dorsal root ganglion (DRG) neurons, thereby contributing to cold hypersensitivity. Our results offer a new understanding of the molecular mechanisms underlying chemotherapy-induced cold hypersensitivity, highlighting KIF15 as a key regulator and a potential therapeutic target for conditions like OIPN.

Keywords

Annexin A2; Cold hypersensitivity; KIF15; OIPN; Oxaliplatin; TRPA1.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z