Inhibition of IRE1 suppresses the catabolic effect of IL-1β on nucleus pulposus cell and prevents intervertebral disc degeneration in vivo
Inhibition of IRE1 suppresses the catabolic effect of IL-1β on nucleus pulposus cell and prevents intervertebral disc degeneration in vivo
复制标题
IRE1 的抑制抑制 IL-1β 对髓核细胞的分解代谢作用并防止体内椎间盘退变
DOI：
10.1016/j.bcp.2022.114932
复制
发表时间：
2022-02-07
影响因子：
5.8
通讯作者：
Li, Feng
中科院分区：
文献类型：
--
作者：
Kang, Honglei;Dong, Yimin;Li, Feng
颈痛和腰痛是导致患者生活质量低下和经济负担沉重的两大疾病，椎间盘退变（IDD）是其发病的重要原因，其发病机制尚不完全清楚。增加的炎性细胞因子包括白细胞介素（IL）-1 β和肿瘤坏死因子（TNF）α和下游信号通路。肌醇需要酶1（IRE 1）是调节内质网（ER）应激的关键酶。研究表明，IRE 1在NF-κ B、PI 3 K/Akt和MAPK信号通路的激活中发挥重要作用。鉴于此，我们进行了一系列的体外和体内实验，以评估IRE 1在IDD的进展中的作用。我们证明IRE 1通路由IL-1 β诱导，抑制IRE 1抑制NP细胞的基质变性，并改善IDD大鼠模型的分级。进一步研究表明，抑制IRE 1可抑制H2 O2诱导的细胞衰老、IL-1 β诱导的细胞活性氧（ROS）水平以及NF-κ B、PI 3 K/Akt和MAPK信号通路的激活。它在NP细胞凋亡和巨噬细胞极化过程中起重要作用。我们的研究结果表明，抑制IRE 1可以抑制NP细胞的变性，并在体内预防IDD。IRE 1可能是IDD治疗的潜在靶点。
Neck pain and low back pain are two of the major diseases, which causes patients a low quantify of life and a heavy economic burden, intervertebral disc degeneration (IDD) contributes to them, and the mechanism is not totally clear. The increased inflammatory cytokines including interleukin (IL)-1 beta and tumor necrosis factor (TNF)alpha and downstream signaling pathways are involved. Inositol requiring enzyme 1 (IRE1) is a crucial enzyme that regulates endoplasmic reticulum (ER) stress. It is reported that IRE1 plays an important role in the activation of NF-kappa B, PI3K/Akt and MAPK signaling pathways. Considering this, we performed a series of experiments in vitro and in vivo to evaluate the role of IRE1 in the progress of IDD. We demonstrated that IRE1 pathway was induced by IL-1 beta, inhibition of IRE1 suppressed the matrix degeneration of NP cells and ameliorated IDD grade in the punctured rat model. Further results indicated that inhibition of IRE1 suppressed H2O2 induced cell senes-cence, IL-1 beta-induced cellular reactive oxygen species (ROS) level and the activation of NF-kappa B, PI3K/Akt and MAPK signaling pathways. It also played a crucial role in the apoptosis of NP cells and the progress of macro-phage polarization. Our findings demonstrated that inhibition of IRE1 could suppress the degeneration of NP cells and prevent IDD in vivo. IRE1 may be a potential target for IDD treatment.