Long Noncoding RNA LINC01619 Regulates MicroRNA-27a/Forkhead Box Protein O1 and Endoplasmic Reticulum Stress-Mediated Podocyte Injury in Diabetic Nephropathy
Long Noncoding RNA LINC01619 Regulates MicroRNA-27a/Forkhead Box Protein O1 and Endoplasmic Reticulum Stress-Mediated Podocyte Injury in Diabetic Nephropathy
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DOI：
10.1089/ars.2017.7278
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发表时间：
2018-08-01
影响因子：
6.6
通讯作者：
Liu, Xiaoting
中科院分区：
文献类型：
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作者：
Bai, Xiaoyan;Geng, Jian;Liu, Xiaoting
目的：长链非编码RNA（lncRNA）的活性改变与microRNA的调控有关。microRNA-27 a（miR-27 a）上调已被证明可诱导糖尿病肾病（DN）中内质网（ER）应激足细胞损伤。在此，我们的目标是探究miR-27 a与长基因间非编码RNA 1619（LINC 01619）和靶基因的相互调节网络。结果：在人类DN肾活检组织中发现LINC 01619下调，并导致蛋白尿和肾功能下降。LINC 01619在足细胞胞质中表达，参与ER应激信号通路。LINC 01619通过充当miR-27 a的“海绵”发挥生物学功能，miR-27 a负靶向叉头盒蛋白O 1（FOXO 1）并激活ER应激。在糖尿病大鼠和高糖培养的足细胞中，LINC 01619引发氧化应激和足细胞损伤，表现为细胞凋亡增加、弥漫性足细胞足突消失和肾功能下降。创新和结论：本研究表明，LINC 01619作为竞争性内源性RNA发挥作用，调节miR-27 a/FOXO 1介导的ER应激和DN足细胞损伤。
Aims: Altered activities of long noncoding RNAs (lncRNAs) have been implicated in the regulation of microRNAs. microRNA-27a (miR-27a) upregulation has been shown to induce endoplasmic reticulum (ER) stress podocyte injury in diabetic nephropathy (DN). Herein, we aim to interrogate the mutually regulated network of miR-27a with long intergenic noncoding RNA 1619 (LINC01619) and the target gene.Results: LINC01619 downregulation was found in human DN renal biopsy tissues and contributed to proteinuria and diminished renal function. LINC01619 was expressed in podocyte cytoplasm and involved in ER stress signaling pathway. LINC01619 exerted biological function by serving as a "sponge'' for miR-27a, which negatively targeted forkhead box protein O1 (FOXO1) and activated ER stress. In diabetic rats and high-glucose cultured podocytes, LINC01619 triggered oxidative stress and podocyte injuries as demonstrated by increased apoptosis, diffuse podocyte foot process effacement, and decreased renal function.Innovation and Conclusion: This study demonstrates that LINC01619 functions as a competing endogenous RNA and regulates miR-27a/FOXO1-mediated ER stress and podocyte injury in DN.