PDF(Pubmed)
Abstract：
Low back pain stands as a significant factor in disability, largely resulting from intervertebral disc degeneration (IVDD). High glucose (HG) levels have been implicated in the pathogenesis of IVDD. However, the detailed mechanism of HG in IVDD is largely unknown. Our clinical results revealed that fibrosis markers such as CTGF, Col1a1, ATF4, and EIF2 are highly expressed in advanced-stage IVDD patients. Stimulation of human annulus fibrosus cells (HAFCs) with HG, but not mannitol, promotes fibrosis protein production. Ingenuity Pathway Analysis in the GSE database found that the mTOR, PKCδ, and NF-κB pathways were significantly changed during IVDD. The mTOR, PKCδ, and NF-κB inhibitors or siRNAs all abolished HG-induced fibrosis protein production. In addition, treatment of HAFCs with HG enhances the activation of mTOR, PKCδ, and NF-κB pathways. Thus, HG facilitates fibrosis in IVDD through mTOR, PKCδ, and NF-κB pathways. These results underscore the critical role of HG as a fibrotic factor in the progression of IVDD.
摘要：
腰背痛是残疾的重要因素，主要由椎间盘退变（IVDD）引起。高葡萄糖（HG）水平与IVDD的发病机理有关。然而,HG在IVDD中的详细机制尚不清楚。我们的临床结果表明，纤维化标志物如CTGF，Col1a1、ATF4和EIF2在晚期IVDD患者中高表达。用HG刺激人纤维环细胞（HAFC），但不是甘露醇,促进纤维化蛋白的产生。GSE数据库中的独创性途径分析发现，PKCδ,和NF-κB通路在IVDD期间显著改变。mTOR,PKCδ,和NF-κB抑制剂或siRNA都消除了HG诱导的纤维化蛋白产生。此外,用HG治疗HAFCs增强了mTOR的激活，PKCδ,和NF-κB通路。因此，HG通过mTOR促进IVDD纤维化，PKCδ,和NF-κB通路。这些结果强调了HG作为纤维化因子在IVDD进展中的关键作用。
