LncRNA SNHG1 knockdown inhibits hyperglycemia induced ferroptosis via miR-16-5p/ACSL4 axis to alleviate diabetic nephropathy

IF 3.2 3区 医学 Journal of Diabetes Investigation Pub Date : 2023-06-14 DOI:10.1111/jdi.14036
Xiangdong Fang, Jianling Song, Yanxia Chen, Shuying Zhu, Weiping Tu, Ben Ke, Lidong Wu
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引用次数: 2

Abstract

Background

Hyperglycemia accelerates the development of diabetic nephropathy (DN) by inducing renal tubular injury. Nevertheless, the mechanism has not been elaborated fully. Here, the pathogenesis of DN was investigated to seek novel treatment strategies.

Methods

A model of diabetic nephropathy was established in vivo, the levels of blood glucose, urine albumin creatinine ratio (ACR), creatinine, blood urea nitrogen (BUN), malondialdehyde (MDA), glutathione (GSH), and iron were measured. The expression levels were detected by qRT-PCR and Western blotting. H&E, Masson, and PAS staining were used to assess kidney tissue injury. The mitochondria morphology was observed by transmission electron microscopy (TEM). The molecular interaction was analyzed using a dual luciferase reporter assay.

Results

SNHG1 and ACSL4 were increased in kidney tissues of DN mice, but miR-16-5p was decreased. Ferrostatin-1 treatment or SNHG1 knockdown inhibited ferroptosis in high glucose (HG)-treated HK-2 cells and in db/db mice. Subsequently, miR-16-5p was confirmed to be a target for SNHG1, and directly targeted to ACSL4. Overexpression of ACSL4 greatly reversed the protective roles of SNHG1 knockdown in HG-induced ferroptosis of HK-2 cells.

Conclusions

SNHG1 knockdown inhibited ferroptosis via the miR-16-5p/ACSL4 axis to alleviate diabetic nephropathy, which provided some new insights for the novel treatment of diabetic nephropathy.

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LncRNA SNHG1敲低通过miR-16-5p/ACSL4轴抑制高血糖诱导的铁下垂,缓解糖尿病肾病
背景:高血糖通过诱导肾小管损伤加速糖尿病肾病(DN)的发展。然而,这一机制尚未得到充分阐述。本文研究了DN的发病机制,以寻求新的治疗策略。方法在体内建立糖尿病肾病模型,测定大鼠血糖、尿白蛋白肌酐比(ACR)、肌酐、尿素氮(BUN)、丙二醛(MDA)、谷胱甘肽(GSH)、铁含量。采用qRT-PCR和Western blotting检测表达水平。H&E、Masson和PAS染色评估肾组织损伤。透射电镜观察线粒体形态。分子相互作用分析使用双荧光素酶报告试验。结果DN小鼠肾组织中SNHG1、ACSL4表达升高,miR-16-5p表达降低。在高糖(HG)处理的HK-2细胞和db/db小鼠中,铁抑素-1治疗或SNHG1敲低可抑制铁下垂。随后,miR-16-5p被证实是SNHG1的靶点,并直接靶向ACSL4。ACSL4过表达大大逆转了SNHG1敲低对hg诱导的HK-2细胞铁凋亡的保护作用。结论SNHG1敲低可通过miR-16-5p/ACSL4轴抑制铁下垂,缓解糖尿病肾病,为糖尿病肾病的新型治疗提供新的思路。
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来源期刊
Journal of Diabetes Investigation
Journal of Diabetes Investigation Medicine-Internal Medicine
自引率
9.40%
发文量
218
期刊介绍: Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).
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