Zhang Hui, Dong Qing-Qing, Shu Hua-Pan, Tu Yu-Chi, Liao Qian-Qian, Yao Li-Jun
Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Arch Biochem Biophys. 2023 Sep 15;746:109728. doi: 10.1016/j.abb.2023.109728. Epub 2023 Aug 24.
Focal segmental glomerulosclerosis (FSGS), a podocyte disease, is the leading cause of end-stage renal disease (ESRD). Nevertheless, the current effective treatment for FSGS is deficient. Curcumin (CUR) is a principal curcuminoid of turmeric, which is a member of the ginger family. Previous studies have shown that CUR has renoprotective effects. However, the mechanism of CUR in anti-FSGS is not clear. This study aimed to explore the mechanism of CUR against FSGS through a combination of network pharmacological methods and verification of experiments. The analysis identified 98 shared targets of CUR against FSGS, and these 98 targets formed a network of protein-protein interactions (PPI). Of these 98 targets, AKT1, TNF, IL-6, VEGFA, STAT3, MAPK3, HIF1A, CASP3, IL1B, and JUN were identified as the hub targets. Molecular docking suggested that the best binding to CUR is MAPK3 and AKT1. Apoptotic process and cell proliferation were identified as the main biological processes of CUR against FSGS by gene ontology (GO) analysis. The most enriched signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was the PI3K-AKT signaling pathway. Western blots and flow cytometry showed that CUR could inhibit adriamycin (ADR) induced apoptosis, oxidative stress damage, and attenuate podocyte epithelial-mesenchymal transition (EMT) by repressing the AKT signaling pathway. Collectively, our study demonstrates that CUR can attenuate apoptosis, oxidative stress damage, and EMT in FSGS in vitro. These results supply a compelling basis for future studies of CUR for the clinical treatment of FSGS.
局灶节段性肾小球硬化（FSGS）是一种足细胞疾病，是终末期肾病（ESRD）的主要原因。然而，目前针对FSGS的有效治疗方法不足。姜黄素（CUR）是姜黄的主要姜黄素类化合物，姜黄是姜科植物的一员。先前的研究表明，CUR具有肾脏保护作用。然而，CUR抗FSGS的机制尚不清楚。本研究旨在通过网络药理学方法与实验验证相结合，探索CUR抗FSGS的机制。分析确定了CUR抗FSGS的98个共同靶点，这98个靶点形成了一个蛋白质-蛋白质相互作用（PPI）网络。在这98个靶点中，AKT1、TNF、IL-6、VEGFA、STAT3、MAPK3、HIF1A、CASP3、IL1B和JUN被确定为枢纽靶点。分子对接表明，与CUR结合最佳的是MAPK3和AKT1。通过基因本体（GO）分析确定凋亡过程和细胞增殖是CUR抗FSGS的主要生物学过程。京都基因与基因组百科全书（KEGG）通路富集分析中最富集的信号通路是PI3K-AKT信号通路。蛋白质免疫印迹和流式细胞术表明，CUR可通过抑制AKT信号通路抑制阿霉素（ADR）诱导的细胞凋亡、氧化应激损伤，并减轻足细胞上皮-间质转化（EMT）。总体而言，我们的研究表明，CUR可在体外减轻FSGS中的细胞凋亡、氧化应激损伤和EMT。这些结果为未来CUR用于FSGS临床治疗的研究提供了有力依据。
