Deguelin Alleviates Renal Tubular Epithelial Cell Injury in Lupus Nephritis by Inhibiting the PI3K/Akt Signaling Pathway.

IF 1.8 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS Assay and drug development technologies Pub Date : 2026-10-12 DOI:10.1177/1540658X261494333

Shiling Zhong, Xunwei Liu, Yunyan Li, Wenying Hao, Yuanling Chen, Jika Zheng, Ling Wu

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Abstract

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus. Circadian rhythm disorders are related to the pathogenesis of LN. This study aims to identify the core circadian rhythm-related genes in LN and identify the potential natural active compounds for LN treatment. In the present study, cyclin A2 (CCNA2) and cyclin-dependent kinase inhibitor 3 (CDKN3) were identified as the core targets most related to the circadian rhythm of LN. Both of them were upregulated in blood and kidney tissue samples in LN and had high diagnostic efficacy. Deguelin had strong binding capabilities with CCNA2 and CDKN3 proteins. Deguelin could dose-dependently alleviate lipopolysaccharide-induced human kidney-2 (HK-2) cell damage, inhibit cell apoptosis and the release of inflammatory factors, downregulate the mRNA and protein expression levels of core genes CCNA2 and CDKN3, and inhibit the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The protective effect of deguelin could be reversed by AKT activator SC79 treatment. In summary, CCNA2 and CDKN3 are core genes related to the circadian rhythm in LN. Deguelin probably alleviates renal tubular epithelial cell injury by modulating the expression levels of core genes CCNA2 and CDKN3, inhibiting the activation of the PI3K/Akt signaling pathway, and thus has the potential to become a therapeutic agent for LN.

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去桂林通过抑制PI3K/Akt信号通路减轻狼疮性肾炎肾小管上皮细胞损伤

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来源期刊

Assay and drug development technologies 医学-生化研究方法

CiteScore

3.60

自引率

0.00%

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审稿时长

>12 weeks

期刊介绍： ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application. ASSAY and Drug Development Technologies coverage includes: -Assay design, target development, and high-throughput technologies- Hit to Lead optimization and medicinal chemistry through preclinical candidate selection- Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis- Approaches to assays configured for gene families, inherited, and infectious diseases- Assays and strategies for adapting model organisms to drug discovery- The use of stem cells as models of disease- Translation of phenotypic outputs to target identification- Exploration and mechanistic studies of the technical basis for assay and screening artifacts