ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy
ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy
复制标题
IgA 肾病中 ELL2 下调并与半乳糖缺陷型 IgA1 相关
DOI：
10.1155/2019/2407067
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Yan Tiekun
中科院分区：
文献类型：
--
作者：
Liu Youxia;Zheng Jie;Zhao Na;Jia Junya;Yan Tiekun
背景半乳糖缺陷型IgA 1（Gd-IgA 1）是伊加肾病的重要致病因素，但其产生机制尚不清楚。RNA聚合酶II的延伸因子（ELL 2）编码超延伸复合物（SEC）的关键组分，驱动分泌特异性IG mRNA的产生。方法收集21例IgAN患者、18例健康对照者和20例非IgAN肾炎患者。使用来自基因表达综合数据集（GEO）的可通过计算机获得的数据比较ELL 2的差异表达。同时检测血清中半乳糖缺陷型IgA 1（Gd-IgA 1）水平与ELL 2表达的关系。最后，通过shELL 2处理实验对上述结果进行了验证。结果IgAN患者外周血中CD 19 + B细胞数量明显高于正常对照组。IgAN患者ELL 2的表达水平显著低于健康对照组和疾病对照组。与目前的结果一致，在来自GEO数据集的微阵列表达谱中观察到IgAN患者中ELL 2表达较低。Pearson相关分析显示ELL 2表达与Gd-IgA 1水平呈负相关。此外，在体外实验中，我们发现在人B淋巴瘤DAKIKI细胞（一种产生IgA 1的细胞系）中ELL 2功能的丧失增加了Gd-IgA 1的水平，这证实了ELL 2调节Gd-IgA 1的水平。结论ELL 2在IgAN中的表达下降与B细胞数和IgA 1糖基化异常呈负相关。
Background Galactose-deficient IgA1 (Gd-IgA1) is an important causal factor in IgA nephropathy; however, the underlying mechanism for the production of Gd-IgA1 is unknown. The elongation factor for RNA polymerase II (ELL2), which encoded a key component of the superelongation complex (SEC), drives secretory-specific Ig mRNA production. Methods We enrolled 21 patients with IgAN, 18 healthy controls, and 20 patients with non-IgAN glomerulonephritis. The differential expression of ELL2 was compared using publically available data from Gene Expression Omnibus (GEO) datasets. The relationship between ELL2 expressions and galactose-deficient IgA1 (Gd-IgA1) levels in serum were also studied. At last, the results were validated by shELL2 treatment experiment. Results We found that the number of CD19+ B cells was increased in IgAN patients compared to healthy controls. The expression level of ELL2 in patients with IgAN was significantly lower than that of healthy control and disease control. Consistent with present results, the lower ELL2 expression in IgAN patients was observed in microarray expression profiles from GEO datasets. Pearson correlation analysis showed that ELL2 expression negatively correlated with Gd-IgA1 levels. Furthermore, in an in vitro experiment, we found that loss of ELL2 function in human B lymphoma DAKIKI cells, an IgA1-producing cell line, increased the levels of Gd-IgA1, which confirmed that ELL2 modulated the levels of Gd-IgA1. Conclusion Our findings implied that decreased ELL2 expression was negatively correlated with the numbers of B cells and aberrant glycosylation of IgA1 in IgAN.