Gene Expression Profiling Identifies Interferon Signalling Molecules and IGFBP3 in Human Degenerative Annulus Fibrosus.
Gene Expression Profiling Identifies Interferon Signalling Molecules and IGFBP3 in Human Degenerative Annulus Fibrosus.
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DOI：
10.1038/srep15662
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发表时间：
2015-10-22
影响因子：
4.6
通讯作者：
Grad S
中科院分区：
文献类型：
--
作者：
Kazezian Z;Gawri R;Haglund L;Ouellet J;Mwale F;Tarrant F;O'Gaora P;Pandit A;Alini M;Grad S
腰痛是导致残疾的主要原因，尤其是对20至50岁的人来说。作为一个昂贵的医疗保健问题，它造成了严重的社会经济负担。目前的手术治疗不能代替正常的椎间盘促进脊柱运动和吸收负荷。再生医学的重点是识别生物标志物和信号通路，以提高我们对椎间盘退变级联的理解，并允许设计特定的治疗方法。我们假设，比较退行性和非退行性椎间盘的微阵列谱将导致识别失调的信号和病理生理目标。从人纤维环细胞中生成微阵列数据集，并使用IPA独创性途径分析进行分析。qRT-PCR验证基因表达值，免疫组织化学鉴定相应蛋白。微阵列分析显示退行性纤维环中有238个差异表达基因。17个失调分子标记显示大于±1.5的log2倍变化。各种失调的细胞功能，包括细胞增殖和炎症反应，被确定。我们发现在退行性纤维环中最重要的典型通路是干扰素通路。本研究提示干扰素- α信号通路激活，IFIT3和IGFBP3上调，可能影响人类退行性椎间盘的细胞功能。
Low back pain is a major cause of disability especially for people between 20 and 50 years of age. As a costly healthcare problem, it imposes a serious socio-economic burden. Current surgical therapies fail to replace the normal disc in facilitating spinal movements and absorbing load. The focus of regenerative medicine is on identifying biomarkers and signalling pathways to improve our understanding about cascades of disc degeneration and allow for the design of specific therapies. We hypothesized that comparing microarray profiles from degenerative and non-degenerative discs will lead to the identification of dysregulated signalling and pathophysiological targets. Microarray data sets were generated from human annulus fibrosus cells and analysed using IPA ingenuity pathway analysis. Gene expression values were validated by qRT-PCR, and respective proteins were identified by immunohistochemistry. Microarray analysis revealed 238 differentially expressed genes in the degenerative annulus fibrosus. Seventeen of the dysregulated molecular markers showed log2-fold changes greater than ±1.5. Various dysregulated cellular functions, including cell proliferation and inflammatory response, were identified. The most significant canonical pathway induced in degenerative annulus fibrosus was found to be the interferon pathway. This study indicates interferon-alpha signalling pathway activation with IFIT3 and IGFBP3 up-regulation, which may affect cellular function in human degenerative disc.