Fig. 5

Hesperetin modulates a panel of DEGs to attenuate senescence and maintain cellular homeostasis. A CISD2 and KRT4 mRNA levels are up-regulated in the HEK001 keratinocytes after hesperetin (Hes) treatment for 48 h. Vehicle (Veh), 0.1% DMSO. B Principal component analysis (PCA, EZinfo 3.0.3 software) of all transcriptomic data (12,103 genes) from vehicle or hesperetin treated HEK001 keratinocytes (n = 3 independent trials). C Volcano plot revealing transcriptome change (Hes vs. Veh). Horizontal line shows the 0.5% false discovery rate (FDR) threshold. Red or blue plots identify genes above the indicated FDR and fold change threshold. A total of 1723 differentially expressed genes (DEGs) were found to be modulated by hesperetin (821 up-regulated and 902 down-regulated genes; Hes vs Veh, Fold change > 1.5 and FDR < 0.005). D The biological processes obtain from Gene Ontology (GO) annotation of transcriptome changes (1723 DEGs) after hesperetin treatment. E A bubble plot illustrating the KEGG pathway enrichment of the DEGs after hesperetin treatment. The grouping of the GO annotation and KEGG pathways were carried out by STRING v11.5 (https://string-db.org/). Pathway FDR < 0.05. F A heatmap illustrating that hesperetin down-regulates the expression of a panel of SASP-related factors (Hes vs Veh, Fold change > 1.1 and p < 0.05). G Canonical pathway analysis by Ingenuity Pathway Analysis (IPA) software based on Hes-mediated transcriptome changes (Hes vs. Veh; pathway p-value < 0.05). Data are presented as mean ± SD. *p < 0.05; **p < 0.005 by Student’s t test. DEGs differentially expressed genes, FC fold change, Redox reduction–oxidation, SASP senescence-associated secretory phenotype, UPR unfolded protein response, UV ultraviolet