Hu Shuai, Bao Hao, Xu Xiaodong, Zhou Xianguang, Qin Weisong, Zeng Caihong, Liu Zhihong
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
FEBS Lett. 2015 Dec 21;589(24 Pt B):4019-25. doi: 10.1016/j.febslet.2015.10.033. Epub 2015 Nov 9.
The number of B cells is increased and the O-glycans of IgA1 are incompletely galactosylated in IgA nephropathy (IgAN). Here we report that expression of phosphatase and tensin homolog (PTEN) and Cosmc is decreased in B cells, and correlates with B cell number and the aberrant glycosylation of IgA1 in IgAN. Patients with IgAN exhibit higher miR-374b in B cells compared to controls. We show that miR-374b targets PTEN and Cosmc by luciferase assays and western blot analysis. Inhibition of miR-374b increased PTEN and Cosmc expression, and prevented cell proliferation and aberrant glycosylation of IgA1, thus representing a new therapeutic approach for IgAN.
在IgA肾病(IgAN)中,B细胞数量增加,IgA1的O-聚糖半乳糖基化不完全。在此我们报告,B细胞中磷酸酶和张力蛋白同源物(PTEN)及Cosmc的表达降低,且与IgAN中B细胞数量及IgA1的异常糖基化相关。与对照组相比,IgAN患者B细胞中的miR-374b水平更高。通过荧光素酶测定和蛋白质印迹分析,我们发现miR-374b靶向PTEN和Cosmc。抑制miR-374b可增加PTEN和Cosmc的表达,并阻止细胞增殖及IgA1的异常糖基化,因此代表了一种针对IgAN的新治疗方法。