The Mechanism of Interaction Between Gold Nanoparticles and Human Dermal Fibroblasts Based on Integrative Analysis of Transcriptomics and Metabolomics Data

Abstract

The aim of this paper was to combine transcriptomics and metabolomics to analyze the mechanism of gold nanoparticles (GNPs) on human dermal fibroblasts (HDFs). First, 20-nm GNPs were prepared, and the differentially expressed genes in HDFs were subsequently screened by transcriptome sequencing technology after 4, 8, and 24 h of treatment with GNPs. By comparing the metabolic pathways in which the metabolites obtained in a previous study were involved, the pathways involving both genes and metabolites were filtered, and the differentially expressed genes and metabolites with upstream and downstream relationships were screened out. The gene–metabolite–metabolic pathway network was further constructed, and the functions of metabolic pathways, genes and metabolites in the important network were analyzed and experimentally verified. The results of transcriptome sequencing experiments showed that 1904, 1216 and 489 genes were differentially expressed in HDFs after 4, 8 and 24 h of treatment with GNPs, and these genes were involved in 270, 235 and 163 biological pathways, respectively. Through the comparison and analysis of the metabolic pathways affected by the metabolites, 7, 3 and 2 metabolic pathways with genes and metabolites exhibiting upstream and downstream relationships were identified. Through analysis of the gene–metabolite–metabolic pathway network, 4 important metabolic pathways, 9 genes and 7 metabolites were identified. Combined with the results of verification experiments on oxidative stress, apoptosis, the cell cycle, the cytoskeleton and cell adhesion, it was found that GNPs regulated the synthesis of downstream metabolites through upstream genes in important metabolic pathways. GNPs inhibited oxidative stress and thus did not induce significant apoptosis, but they exerted effects on several cellular functions, including arresting the cell cycle and affecting the cytoskeleton and cell adhesion.