Department of Nephrology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Chronic Kidney Disease and Blood Purification, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, P.R. China.
Pediatric Department, Shunyi Women's and Children's Hospital of Beijing Children's Hospital, Beijing 101300, P.R. China.
Mol Med Rep. 2020 May;21(5):2260-2266. doi: 10.3892/mmr.2020.11015. Epub 2020 Mar 9.
The aim of the present study was to investigate the effect of microRNAs (miRNAs) on the expression level of core1β3‑galactosyltransferase‑specific molecular chaperone (COSMC) in immunoglobulin A nephropathy (IgAN). miRNA expression levels were determined in pediatric patients with IgAN (IgAN group), in patients with other renal diseases (control group) and healthy pediatrics (control group). The target miRNAs of COSMC were investigated in the present study. Western blot analysis was performed to examine the effects of miRNAs on COSMC expression levels. In addition, galactose‑deficient IgA1 (Gd‑IgA1) expression levels were detected following the addition of miRNA‑196b. The present results suggested that the expression levels of 205 miRNAs significantly differed between the IgAN and healthy control groups. The present results also suggested that miRNA‑196b and miRNA‑33a‑3p targeted COSMC, and that miRNA‑196b expression in B lymphocytes was significantly higher in the IgAN group compared with the control group (P<0.0001). However, COSMC expression level was significantly downregulated in isolated B lymphocytes transfected with miRNA‑196b mimics, but Gd‑IgA1 expression levels were increased. Therefore, miRNA‑196b may play a role in the formation of Gd‑IgA1 and IgAN pathogenesis via COSMC regulation.
本研究旨在探讨微小 RNA(miRNA)对免疫球蛋白 A 肾病(IgAN)中核心 1β3-半乳糖基转移酶特异性分子伴侣(COSMC)表达水平的影响。测定了儿科 IgAN 患者(IgAN 组)、其他肾脏疾病患者(对照组)和健康儿童(对照组)的 miRNA 表达水平。本研究还探讨了 COSMC 的靶 miRNAs。通过 Western blot 分析检测 miRNA 对 COSMC 表达水平的影响。此外,添加 miRNA-196b 后检测缺乏半乳糖的 IgA1(Gd-IgA1)表达水平。结果表明,IgAN 组和健康对照组之间 205 种 miRNA 的表达水平显著不同。结果还表明,miRNA-196b 和 miRNA-33a-3p 靶向 COSMC,且 IgAN 组 B 淋巴细胞中 miRNA-196b 的表达明显高于对照组(P<0.0001)。然而,转染 miRNA-196b 模拟物的分离 B 淋巴细胞中 COSMC 表达水平明显下调,但 Gd-IgA1 表达水平升高。因此,miRNA-196b 可能通过调节 COSMC 参与 Gd-IgA1 的形成和 IgAN 的发病机制。