Silencing long noncoding RNA-CES1P1 suppresses glomerular endothelial cell inflammation in diabetic nephropathy
Silencing long noncoding RNA-CES1P1 suppresses glomerular endothelial cell inflammation in diabetic nephropathy
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沉默长链非编码RNA-CES1P1可抑制糖尿病肾病的肾小球内皮细胞炎症
DOI：
10.1016/j.intimp.2022.108820
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Hong Qiao
中科院分区：
文献类型：
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作者：
Xiaona Zhang;Long Ren;Jiaxing Wei;Yanan Ni;Lulu Sun;Xiaoyu Zhao;Yaguang Zhang;Hong Qiao
糖尿病肾病（diabetic nephropathy，DN）已成为世界范围内终末期肾病的主要病因。炎症与DN的发生、发展密切相关，长链非编码RNA（lncRNA）参与了炎症过程的调控。本研究以C57 BL/6小鼠和人脐静脉内皮细胞（HUVECs）为实验材料，探讨了lncRNA-CES 1 P1在DN中的作用及其机制。在C57 BL/6小鼠体内实验性腹腔注射链脲佐菌素（STZ）构建糖尿病（DM）模型，导致肾脏组织中lncRNA-CES 1 P1表达增加，miR-214- 3 p表达减少，并产生肾脏炎症和蛋白尿。外源性敲低lncRNA-CES 1 P1表达可减少肾脏炎症浸润。在体外实验中，使用高糖（HG）刺激HUVECs细胞显示lncRNA-CES 1 P1的表达增加，miR-214- 3 p的表达减少，以及炎症因子IL-17、IκB、NF-κB和IL-6的表达增加。荧光素酶报告基因分析显示miR-214- 3 p与lncRNA-CES 1 P1和IL-17相互作用的直接靶点。这些结果表明，高血糖通过诱导lncRNA-CES 1 P1抑制miR-214- 3 p，其促进炎性因子IL-17、IκB、NF-κB和IL-6的表达，最终导致DN的发展。干扰lncRNA-CES 1 P1可减轻高血糖所致的DN。
Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide. Inflammation is associated with the occurrence and development of DN, and long noncoding RNAs (lncRNAs) are involved in the regulation of inflammatory processes. This study aims to determine the role and mechanism of lncRNA-CES1P1 in DN.C57BL/6 mice and human umbilical vein endothelial cells (HUVECs) were used for this experimental study. In vivo experimental intraperitoneal injection of streptozotocin (STZ) to construct a diabetes mellitus (DM) model in C57BL/6 mice caused increased expression of lncRNA-CES1P1, decreased expression of miR-214-3p in kidney tissue, and produced renal inflammation and proteinuria. Exogenous knockdown of lncRNA-CES1P1 expression decreased renal inflammatory infiltration. In vitro experiments using high glucose (HG) stimulation of HUVECs cell revealed increased expression of lncRNA-CES1P1, decreased expression of miR-214-3p, and increased expression of the inflammatory factors IL-17, IκB, NF-κB, and IL-6. Luciferase reporter assays showed direct targets of miR-214-3p interaction with lncRNA-CES1P1 and IL-17. These results suggest that hyperglycemia represses miR-214-3p by inducing lncRNA-CES1P1, which promotes the expression of the inflammatory factors IL-17, IκB, NF-κB and IL-6 ultimately leading to the development of DN. Interfering with lncRNA-CES1P1 can reduce hyperglycemia-induced DN.