Department of Neurosurgery, Trakya University School of Medicine, Edirne, Turkey.
Department of Medical Biology, Trakya University School of Medicine, Edirne, Turkey.
World Neurosurg. 2020 May;137:e506-e516. doi: 10.1016/j.wneu.2020.02.024. Epub 2020 Feb 12.
Although previous studies have reported the expression of JAK1, STAT3, and phosphorylated STAT3 in hypertrophied ligamentum flavum (LF), the role of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway in hypertrophied LF has not been fully elucidated. The aim of this study was to identify the important JAK/STAT gene expression patterns of the 3 main receptors involved in this pathway: interferon (IFN)-γ receptor (IFN-γR), IFN-α receptor (IFNAR), and interleukin (IL)-6 receptor (IL-6R).
The human LF specimens were obtained from 28 patients who underwent lumbar spine surgery for either degenerative lumbar canal stenosis (DLCS) (n = 28) or lumbar disc herniation (LDH) (n = 20). In this design, patients with LDH served as the control group. The degree of fibrosis was demonstrated by Masson's trichrome staining. The location and expression profiling of the JAK/STAT pathway were analyzed by quantitative real-time polymerase chain reaction and Western blotting. The thickness of the LF was measured with axial T1-weighted magnetic resonance imaging.
The most severe fibrotic changes were on the dorsal side of the LF. IL-6 and IFN-I expression levels were significantly increased on the dorsal side of the LF. While expression levels of IL-6R and IFNAR on the dural and dorsal side were significantly higher in the DLCS samples, IFN-γR and endothelial epidermal growth factor receptor in LF samples showed a significant increase only on the dorsal side. JAK/STAT genes were significantly expressed, especially on the dorsal side.
Our data suggest that IFNAR- and IL-6R-dependent JAK/STAT signaling pathways may be significant targets in drug development strategies for the treatment of LF hypertrophy.
尽管先前的研究已经报道了 JAK1、STAT3 和磷酸化 STAT3 在肥厚性黄韧带（LF）中的表达，但 Janus 激酶-信号转导和转录激活因子（JAK/STAT）信号通路在肥厚性 LF 中的作用尚未完全阐明。本研究旨在确定该通路中涉及的 3 个主要受体（干扰素（IFN）-γ 受体（IFN-γR）、IFN-α 受体（IFNAR）和白细胞介素（IL）-6 受体（IL-6R）的重要 JAK/STAT 基因表达模式。
从因退行性腰椎管狭窄症（DLCS）（n=28）或腰椎间盘突出症（LDH）（n=20）而行腰椎脊柱手术的 28 例患者中获得人 LF 标本。在这种设计中，LDH 患者作为对照组。Masson 三色染色显示纤维化程度。通过定量实时聚合酶链反应和 Western blot 分析 JAK/STAT 通路的位置和表达谱。LF 的厚度通过轴向 T1 加权磁共振成像测量。
LF 的背侧纤维变性最严重。LF 背侧的 IL-6 和 IFN-I 表达水平显著增加。虽然在 DLCS 样本中，LF 背侧的 IL-6R 和 IFNAR 表达水平显著升高，但只有 LF 样本中的 IFN-γR 和内皮表皮生长因子受体在背侧显著增加。JAK/STAT 基因表达显著，特别是在背侧。
我们的数据表明，IFNAR 和 IL-6R 依赖性 JAK/STAT 信号通路可能是治疗 LF 肥大药物开发策略的重要靶点。
