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[1]黄海,列才华,梁兰青,等.细胞因子对IgA肾病患者IgA1 O-糖基化的影响及相关机制研究[J].医学研究与战创伤救治(原医学研究生学报),2019,21(01):44-48.[doi:10.3969/j.issn.1672-271X.2019.01.010]
 HUANG Hai,LIE Cai-hua,LIANG Lan-qing,et al.Effects of cytokines on IgA1 O-glycosylation in IgAN and its related mechanisms[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2019,21(01):44-48.[doi:10.3969/j.issn.1672-271X.2019.01.010]
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细胞因子对IgA肾病患者IgA1 O-糖基化的影响及相关机制研究()

《医学研究与战创伤救治》(原医学研究生学报)[ISSN:1672-271X/CN:32-1713/R]

卷:
第21卷
期数:
2019年01期
页码:
44-48
栏目:
临床研究
出版日期:
2019-01-20

文章信息/Info

Title:
Effects of cytokines on IgA1 O-glycosylation in IgAN and its related mechanisms
作者:
黄海列才华梁兰青屈姗郭志勇
作者单位:200433上海,海军军医大学长海医院肾内科(黄海、郭志勇);830002乌鲁木齐,新疆军区总医院肾内科(列才华、梁兰青、屈姗)
Author(s):
HUANG Hai1 LIE Cai-hua 2 LIANG Lan-qing 2 QU Shan 2 GUO Zhi-yong 1
(1.Department of Nephrology, Changhai Hospital, Naval Military Medical University, Shanghai 200433,China;2. Department of Nephrology, Xinjiang Military Area General Hospital, Urumqi 830002, Xinjiang, China)
关键词:
糖基化IgA肾病免疫球蛋白A1O-聚糖
Keywords:
glycosylationIgA nephropathyIgA1O-glycans
分类号:
R392.8
DOI:
10.3969/j.issn.1672-271X.2019.01.010
文献标志码:
A
摘要:
目的 探讨细胞因子对IgA肾病(IgAN)患者IgA1 O-糖基化的影响,分析相关影响机制。方法 选取2017年4-10月于新疆军区总医院肾内科就诊的IgAN患者35例作为IgAN组,招募同期于医院就诊的健康志愿者15例作为对照组。对2组人群的IgA1分泌细胞与细胞因子共培养,观察细胞因子对IgA1 O-糖基化的影响及对C1GalT1和ST6GalNAc-Ⅱ酶活性和表达基因的影响;采用siRNA敲低技术,干扰IgA1分泌细胞中C1GALT1和(或)ST6GALNAC2的表达,验证细胞因子与之相关性;开发基于假设的体外测定,进一步诠释细胞因子对IgAN患者IgA1 O-糖基化的影响机制。结果 IL-6可显著促进IgA1的产生(P<0.05),显著增加IgA1半乳糖缺乏(P<0.05),对IgAN患者作用更明显(P<0.05)。IL-6显著增加ST6GalNAc-II活性(P<0.05),显著降低C1GalT1活性(P<0.01);IL-6显著上调ST6GALNAC2基因表达,同时显著降低C1GALT1和COSMC基因表达(P<0.01),与测定酶活性变化一致。siRNA干扰技术使每个基因mRNA水平降低了65%~75%。C1GALT1敲除显著促进IgAN细胞和对照组的IgA1半乳糖缺乏(P<0.05);ST6GALNAC2敲减仅明显降低IgAN细胞分泌的IgA1半乳糖缺乏(P<0.05),敲低后分泌的IgA1半乳糖含量与对照组相当。IgA1 O-聚糖的有效半乳糖基化可以通过过早的唾液酸化实质性降低。结论 细胞因子IL-6通过对IgAN患者ST6GALNAC2 和C1GALT1酶的活性及其基因表达调节,上调IgAN患者IgA1的半乳糖缺乏,进而增加免疫复合物形成和导致疾病恶化。
Abstract:
Objective To investigate the effects of cytokines on IgA1 O-glycosylation in IgAN patients and to analyze the related mechanisms.Methods 35 IgAN patients who were admitted to the Department of Nephrology, General Hospital of Xinjiang Military Region from April to October 2017 were selected as IgAN group, and 15 healthy volunteers who were admitted to our hospital at the same time were recruited as Controls group. The co-culture of IgA1-secreting cells from IgAN and Controls co-cultured with cytokines to observe the effects of cytokines on IgA1 O-glycosylation and the differences in cytokines on the activity of C1GalT1 and ST6GalNAc-II and the expression of genes;SiRNA knockdown technique was used to interfere with the expression of C1GALT1 and / or ST6GALNAC2 in IgA1-secreting cells from IgAN patients and healthy controls respectively to verify the correlation between cytokines;The hypothesis-based in vitro assay was developed to further elucidate the mechanism by which cytokines affect IgA1 O-glycosylation in IgAN patients.Results IL-6 significantly increased the production of IgA1 (P<0.05), and promoted the expression of IgA1 in patients with IgAN (P<0.05);IL-6 significantly increased the secretion of IgA1-galactose in both groups. The effect was more significant (P<0.01). IL-6 significantly increased the activity of STGGalNAc-II (P<0.05) and significantly decreased the activity of C1GalT1 (P<0.01);IL-6 significantly increased the expression of ST6GALNAC2 gene and significantly decreased the expression of C1GALT1 and COSMC genes (P

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备注/Memo

备注/Memo:
基金项目:新疆维吾尔自治区自然科学基金(2015211C236)
更新日期/Last Update: 2019-01-20