Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, University of Catania, Italy.
Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, University of Catania, Italy.
Mol Cell Neurosci. 2017 Dec;85:162-169. doi: 10.1016/j.mcn.2017.10.001. Epub 2017 Oct 6.
Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the degeneration and death of upper (UMN) and lower (LMN) motor neurons. In the last decade, it has been shown that Chitinases are an important prognostic indicator of neuro-inflammatory damage induced by microglia and astrocytes.
We analyzed microarray datasets obtained from the Array Express in order to verify the expression levels of CHI3L1 and CHI3L2 in motor cortex biopsies of sALS patients with different survival times. We also divided the sALS patients into smokers and non-smokers. In order to extend our analysis, we explored two additional microarray datasets, GSE833 and GSE26927, of post-mortem spinal cord biopsies from sALS patients.
The analysis showed that CHI3L1 and CHI3L2 expression levels were significantly upregulated in the motor cortex of sALS patients, compared to the healthy controls. Moreover, their expression levels were negatively correlated with survival time. Interesting results were obtained when we compared the expression levels of Chitinases among smokers. We showed that CHI3L1 and CHI3L2 were significantly upregulated in sALS smokers compared to non-smokers. Furthermore, we found that four genes belonging to the Chitinases network (SERPINA3, C1s, RRAD, HLA-DQA1) were significantly upregulated in the motor cortex of sALS patients and positively correlated with Chitinases expression levels. Similar results were obtained during the exploration of the two-microarray dataset.
This study suggests that CHI3L1 and CHI3L2 are associated with the progression of neurodegeneration in motor cortex and spinal cord of sALS patients.
肌萎缩侧索硬化症（ALS）是一种快速进展的神经退行性疾病，其特征是上运动神经元（UMN）和下运动神经元（LMN）的退化和死亡。在过去的十年中，已经表明几丁质酶是小胶质细胞和星形胶质细胞诱导的神经炎症损伤的重要预后指标。
我们分析了从 ArrayExpress 获取的微阵列数据集，以验证不同存活时间的 sALS 患者运动皮层活检中 CHI3L1 和 CHI3L2 的表达水平。我们还将 sALS 患者分为吸烟者和非吸烟者。为了扩展我们的分析，我们探索了另外两个微阵列数据集，GSE833 和 GSE26927，来自 sALS 患者死后的脊髓活检。
分析表明，与健康对照相比，sALS 患者运动皮层中 CHI3L1 和 CHI3L2 的表达水平显著上调。此外，它们的表达水平与存活时间呈负相关。当我们比较吸烟者之间几丁质酶的表达水平时，我们得到了有趣的结果。我们表明，与非吸烟者相比，sALS 吸烟者中 CHI3L1 和 CHI3L2 的表达水平显著上调。此外，我们发现属于几丁质酶网络的四个基因（SERPINA3、C1s、RRAD、HLA-DQA1）在 sALS 患者的运动皮层中显著上调，并与几丁质酶的表达水平呈正相关。在探索两个微阵列数据集的过程中也得到了类似的结果。
这项研究表明，CHI3L1 和 CHI3L2 与 sALS 患者运动皮层和脊髓神经退行性变的进展有关。
