Berberine Inhibits Migration and Apoptosis of Rat Podocytes in Diabetic Nephropathy via the Novel lncRNA LOC102549726 Related Pathway.

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Phytotherapy Research Pub Date : 2025-03-01 Epub Date: 2025-02-06 DOI:10.1002/ptr.8452
Chen Wang, Hao Wu, Yongsheng Xie, Jiajia Wang, Lingzhi Huang, Xiayun Ni, Shujun Deng, Yang Zhang, Xinyi Chen, Huihui Zhang, Siming Yuan, Liqin Tang
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引用次数: 0

Abstract

Background: Diabetic nephropathy (DN) stands as one of the most severe complications of diabetes. Podocytes injury, particularly its attachment to the lateral glomerular basement membrane, serves as a crucial indicator of DN. Growing evidence suggests that berberine (BBR) can mitigate the onset and progression of DN. However, the molecular mechanisms through which BBR exerts its beneficial effects in the treatment of DN remain incompletely elucidated.

Purpose: To explore the underlying mechanisms by which BBR exerts its therapeutic effects in DN.

Methods: High-throughput lncRNA sequencing on the renal cortex of both the DN model group and the normal SD group was performed to dig for differentially expressed lncRNAs. The expression of LOC102549726 was evaluated using qPCR. The biological functions of LOC102549726 were analyzed in podocyets and DN rats. The bioinformatics techniques, qPCR and WB were used to explore the potential molecular mechanisms.

Results: We found that lncRNA LOC102549726 was highly expressed in renal cortex of DN rats and podocytes subjected to high glucose conditions. Silencing LOC102549726 inhibited migration and apoptosis of podocytes. Mechanistically, LOC102549726 was identified as a facilitator of the expression of EGF and forkhead box O1 (FOXO1). BBR, a known therapeutic agent for DN, exhibited the ability to diminish the level of LOC102549726, EGF and FOXO1 in both DN rats and podocytes.

Conclusion: Our findings suggested that BBR suppresses migration and apoptosis of podocytes in DN through targeting the LOC102549726/EGF/FOXO1 axis. This sheds light on a potential therapeutic avenue for mitigating the impact of DN on podocyte function.

小檗碱通过新的lncRNA LOC102549726相关通路抑制糖尿病肾病大鼠足细胞的迁移和凋亡
背景:糖尿病肾病(DN)是糖尿病最严重的并发症之一。足细胞损伤,特别是其附着在肾小球外侧基底膜上,是DN的一个重要指标。越来越多的证据表明,小檗碱(BBR)可以减轻DN的发生和进展。然而,BBR在治疗DN中发挥其有益作用的分子机制尚未完全阐明。目的:探讨BBR治疗DN的作用机制。方法:对DN模型组和正常SD组肾皮质进行高通量lncRNA测序,寻找差异表达的lncRNA。采用qPCR检测LOC102549726的表达。分析LOC102549726在足鼠和DN大鼠中的生物学功能。利用生物信息学、qPCR和WB等技术对其潜在的分子机制进行了探讨。结果:我们发现lncRNA LOC102549726在高糖条件下DN大鼠肾皮质和足细胞中高表达。沉默LOC102549726抑制足细胞迁移和凋亡。机制上,LOC102549726被鉴定为EGF和叉头盒01 (fox01)表达的促进者。BBR是一种已知的DN治疗剂,在DN大鼠和足细胞中均表现出降低LOC102549726、EGF和FOXO1水平的能力。结论:我们的研究结果表明,BBR通过靶向LOC102549726/EGF/FOXO1轴抑制DN足细胞的迁移和凋亡。这揭示了减轻DN对足细胞功能影响的潜在治疗途径。
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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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