JAG ‐1/Notch signaling axis in the spinal cord contributes to bone cancer pain in rats

Schematic showing that jagged1 (JAG-1)/Notch-1-mediated astrocyte-neuron interaction contributes to the maintenance of bone cancer-induced pain hypersensitivity: Bone cancer pain (BCP) induces up-regulation of JAG-1 expression in spinal astrocytes. Astrocyte JAG-1 regulates neuronal activation through the Notch signaling pathway and up-regulates hairy and enhancer of split homolog-1(Hes-1) expression by inducing the recruitment of Notch intracellular domain (NICD) to the RBP-J/CSL-binding site located within the Hes-1 promoter sequence, which contributes to BCP. AbstractNotch signal plays an important role in regulating cell –cell interactions with the adjacent cells. However, it remains unknown whether Jagged1 (JAG-1) mediated Notch signaling regulates bone cancer pain (BCP) via the spinal cell interactions mechanism. Here, we showed that intramedullary injection of Walker 256 breast cancer cells increased the expres sion of JAG-1 in spinal astrocytes and knockdown of JAG-1 reduced BCP. The supplementation of exogenous JAG-1 to the spinal cord induced BCP-like behavior and promoted expression of c-Fos and hairy and enhancer of split homolog-1 (Hes-1) in the spinal cord of the naïve rats. These effects were reve rsed when the rats were administered intrathecal injections of N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). The intrathecal injection of DAPT reduced BCP and inhibited Hes-1 and c-Fos expression in the spinal cord. Furthermore, our ...

Source: Journal of Neurochemistry - July 9, 2023 Category: Neuroscience Authors: Jie Fu, Baoxia Zhao, Ge Luo, Huadong Ni, Longsheng Xu, Qiuli He, Miao Xu, Chengfei Xu, Yahui Wang, Chaobo Ni, Ming Yao Tags: ORIGINAL ARTICLE Source Type: research