LncRNA GAS5 reduces blood glucose levels and alleviates renal fibrosis in diabetic nephropathy by regulating the miR-542-3p/ERBB4 axis.

IF 3.9 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Diabetology & Metabolic Syndrome Pub Date : 2025-01-23 DOI:10.1186/s13098-025-01593-z

Qinghua Yin, Na Guo, Ruoxi Liao

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Abstract

Objective: The present study was implemented to unravel the effect of lncRNA GAS5 on renal fibrosis induced by diabetic nephropathy (DN) by regulating the miR-542-3p/ERBB4 axis.

Methods: db/db mice were injected with lncRNA GAS5 high expression or miR-542-3p low expression related vectors. Biochemical experiments were performed to assess blood glucose level and urine protein concentration. HE, TUNEL and Masson stainings were employed to observe the cellular morphology, apoptosis, and fibrosis of renal tissues, respectively. ELISA was executed to examine the levels of IL-1β, IL-6, and TNF-α; and the superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) activities were evaluated. Bioinformatics analysis, dual-luciferase and RIP assays were performed to verify the relationship between lncRNA GAS5 and miR-542-3p, and miR-542-3p and ERBB4.

Results: LncRNA GAS5 and ERBB4 were lowly expressed and miR-542-3p was highly expressed in the renal tissues of DN mice. Overexpression of lncRNA GAS5 or low-expression of miR-542-3p diminished DN-induced renal fibrosis. LncRNA GAS5 could bind to miR-542-3p and miR-542-3p further modulating ERBB4 expression. Up-regulation of miR-542-3p neutralized the suppressive effect of lncRNA GAS5 overexpression and down-regulation of ERBB4 also counteracted the inhibitory impact of down-regulation of miR-542-3p on renal fibrosis in DN mice.

Conclusion: Up-regulation of lncRNA GAS5 alleviates renal fibrosis in DN mice via down-regulation of miR-542-3p and up-regulation of ERBB4.

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LncRNA GAS5通过调节miR-542-3p/ERBB4轴降低血糖水平，缓解糖尿病肾病肾纤维化。

目的：本研究旨在揭示lncRNA GAS5通过调控miR-542-3p/ERBB4轴在糖尿病肾病（DN）诱导的肾纤维化中的作用。方法：向db/db小鼠注射高表达的lncRNA GAS5或低表达的miR-542-3p相关载体。生化实验测定血糖水平和尿蛋白浓度。HE染色、TUNEL染色、Masson染色分别观察大鼠肾组织的细胞形态、凋亡和纤维化情况。ELISA法检测IL-1β、IL-6、TNF-α水平；测定其超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和丙二醛（MDA）活性。通过生物信息学分析、双荧光素酶和RIP实验验证lncRNA GAS5与miR-542-3p、miR-542-3p与ERBB4之间的关系。结果：LncRNA GAS5、ERBB4在DN小鼠肾组织中低表达，miR-542-3p高表达。lncRNA GAS5过表达或miR-542-3p低表达可减少dn诱导的肾纤维化。LncRNA GAS5可以结合miR-542-3p和miR-542-3p进一步调节ERBB4的表达。miR-542-3p上调可中和lncRNA GAS5过表达的抑制作用，ERBB4下调可抵消miR-542-3p下调对DN小鼠肾纤维化的抑制作用。结论：上调lncRNA GAS5通过下调miR-542-3p和上调ERBB4来缓解DN小鼠肾纤维化。

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来源期刊

Diabetology & Metabolic Syndrome ENDOCRINOLOGY & METABOLISM-

CiteScore

6.20

自引率

0.00%

发文量

170

审稿时长

7.5 months

期刊介绍： Diabetology & Metabolic Syndrome publishes articles on all aspects of the pathophysiology of diabetes and metabolic syndrome. By publishing original material exploring any area of laboratory, animal or clinical research into diabetes and metabolic syndrome, the journal offers a high-visibility forum for new insights and discussions into the issues of importance to the relevant community.