通过 miR-30e-5p/SOX4 轴沉默 LncRNA SNHG14 可减轻糖尿病肾病的进展。

IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
YunXia Wang, JiaJia Yang, Chun Wu, Yuqin Guo, Yuan Ding, Xiujuan Zou
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引用次数: 0

摘要

背景:糖尿病肾病(DN)是一种糖尿病并发症。据报道,LncRNA参与了DN的病理生理学过程。本文探讨了lncRNA小核RNA宿主基因14(SNHG14)在DN中的功能和机制:方法:利用链脲佐菌素(STZ)诱导的DN小鼠模型和高糖(HG)处理的人间质细胞(MCs)检测SNHG14的表达。应用SNHG14沉默质粒检测SNHG14对HG处理的MCs增殖和纤维化的功能。利用生物信息学工具预测了SNHG14的潜在靶点,并通过荧光素酶报告、RNA pulldown和北印迹实验进行了验证。通过向DN小鼠注射携带sh-SNHG14的腺病毒载体,检测了SNHG14在DN体内的功能作用。对 DN 小鼠的血清肌酐、血尿素氮、血糖、24 小时蛋白尿、相对肾脏重量和肾脏病理变化进行了检测:结果:SNHG14在DN小鼠肾脏和经HG处理的MCs中表达升高。结果:SNHG14在DN小鼠肾脏和HG处理的MCs中表达升高,沉默SNHG14可抑制HG刺激下MCs的增殖和纤维化。SNHG14 与 miR-30e-5p 结合可上调 SOX4 的表达。在拯救实验中,SOX4的升高减弱了HG处理的MCs中SNHG14沉默的效果,而SOX4沉默则逆转了SNHG14过表达的效果。在体内研究中,下调SNHG14能显著改善DN小鼠的肾损伤和肾间质纤维化:结论:沉默 SNHG14 可减轻 DN 小鼠的肾损伤,并通过 miR-30e-5p/SOX4 轴减少 HG 刺激 MCs 的增殖和纤维化表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

LncRNA SNHG14 silencing attenuates the progression of diabetic nephropathy via the miR-30e-5p/SOX4 axis

LncRNA SNHG14 silencing attenuates the progression of diabetic nephropathy via the miR-30e-5p/SOX4 axis

Background

Diabetic nephropathy (DN) is a diabetic complication. LncRNAs are reported to participate in the pathophysiology of DN. Here, the function and mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) in DN were explored.

Methods

Streptozotocin (STZ)-induced DN mouse models and high glucose (HG)-treated human mesangial cells (MCs) were used to detect SNHG14 expression. SNHG14 silencing plasmids were applied to examine the function of SNHG14 on proliferation and fibrosis in HG-treated MCs. Potential targets of SNHG14 were predicted using bioinformatics tools and verified by luciferase reporter, RNA pulldown, and northern blotting assays. The functional role of SNHG14 in DN in vivo was detected by injection with adenoviral vector carrying sh-SNHG14 into DN mice. Serum creatinine, blood urea nitrogen, blood glucose, 24-h proteinuria, relative kidney weight, and renal pathological changes were examined in DN mice.

Results

SNHG14 expression was elevated in the kidneys of DN mice and HG-treated MCs. SNHG14 silencing inhibited proliferation and fibrosis of HG-stimulated MCs. SNHG14 bound to miR-30e-5p to upregulate SOX4 expression. In rescue assays, SOX4 elevation diminished the effects of SNHG14 silencing in HG-treated MCs, and SOX4 silencing reversed the effects of SNHG14 overexpression. In in vivo studies, SNHG14 downregulation significantly ameliorated renal injuries and renal interstitial fibrosis in DN mice.

Conclusions

SNHG14 silencing attenuates kidney injury in DN mice and reduces proliferation and fibrotic phenotype of HG-stimulated MCs via the miR-30e-5p/SOX4 axis.

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来源期刊
Journal of Diabetes
Journal of Diabetes ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
2.20%
发文量
94
审稿时长
>12 weeks
期刊介绍: Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation. The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.
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