Tang Ying, Liu Zihan, Wu Xianhe, He Zhengqing, Yang Fan, Chen Huiqin, Chen Yu, Zheng Qibin, Huang Yang, Chen Aiqin, Lin Chun
Pain Research Institute, School of Basic Medical Sciences, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Medical University, Fuzhou, Fujian, PR China.
College of Medicine, Pingdingshan University, Pingdingshan, Henan, PR China.
Mol Pain. 2025 Jan-Dec;21:17448069251358692. doi: 10.1177/17448069251358692. Epub 2025 Jul 3.
Irritable bowel syndrome (IBS) is characterized by chronic visceral pain, but its molecular mechanisms remain controversial, hindering effective treatment. This research is to investigate the role of lncRNA RT1-CE10 in chronic visceral pain associated with IBS and to elucidate the underlying molecular mechanisms. An IBS rat model was developed in rats, and RNA-Seq analysis was conducted to assess lncRNA RT1-CE10 expression. The subcellular localization of lncRNA RT1-CE10 and its co-localization with ATP1a3 in spinal cord neurons were examined. AAV was used to over-express lncRNA RT1-CE10 in the spinal cord to study its effects on ATP1a3 levels and pain response, with knockdown experiments to evaluate the impact of reduced lncRNA RT1-CE10. The RNA-Seq analysis revealed a significant down-regulation of lncRNA RT1-CE10 in IBS rats. The lncRNA was found to be expressed in both the cytoplasm and the nucleus and to co-localize with ATP1a3 in spinal cord neurons. Over- expression of lncRNA RT1-CE10 via AAV-lncRT1-CE10 increased ATP1a3 levels and alleviated visceral pain response, while knockdown of lncRNA RT1-CE10 decreased ATP1a3 levels and enhanced visceral pain response. Additionally, a marked decrease in ATP1a3 expression was observed in the spinal cords of IBS rats. Modulating ATP1a3 expression either through over-expression or knockdown could alleviate or aggravate chronic visceral pain, respectively. LncRNA RT1-CE10, which is lowly expressed in the spinal cord of IBS rats, interacts with ATP1a3 and influences chronic visceral pain. These findings could lead to the development of targeted therapeutic interventions for IBS.
肠易激综合征（IBS）以慢性内脏疼痛为特征，但其分子机制仍存在争议，这阻碍了有效治疗。本研究旨在探讨长链非编码RNA RT1-CE10在与IBS相关的慢性内脏疼痛中的作用，并阐明其潜在的分子机制。在大鼠中建立了IBS大鼠模型，并进行RNA测序分析以评估长链非编码RNA RT1-CE10的表达。检测了长链非编码RNA RT1-CE10在脊髓神经元中的亚细胞定位及其与ATP1a3的共定位。使用腺相关病毒（AAV）在脊髓中过表达长链非编码RNA RT1-CE10，以研究其对ATP1a3水平和疼痛反应的影响，并进行敲低实验以评估长链非编码RNA RT1-CE10减少的影响。RNA测序分析显示IBS大鼠中长链非编码RNA RT1-CE10显著下调。发现该长链非编码RNA在细胞质和细胞核中均有表达，并在脊髓神经元中与ATP1a3共定位。通过AAV-lncRT1-CE10过表达长链非编码RNA RT1-CE10可提高ATP1a3水平并减轻内脏疼痛反应，而敲低长链非编码RNA RT1-CE10则降低ATP1a3水平并增强内脏疼痛反应。此外，在IBS大鼠的脊髓中观察到ATP1a3表达明显降低。通过过表达或敲低来调节ATP1a3表达可分别减轻或加重慢性内脏疼痛。长链非编码RNA RT1-CE10在IBS大鼠脊髓中低表达，它与ATP1a3相互作用并影响慢性内脏疼痛。这些发现可能会导致针对IBS的靶向治疗干预措施的开发。
