Microarray analysis of lipopolysaccharide-induced endotoxemia in the cochlea

• Published in: Gene Vol. 823; p. 146347
• Main Authors: Lee, Sang-Yeon, Kim, Songmi, Han, Kyudong, Woong Choi, Jin, Byung Chae, Ho, Yeon Choi, Da, Min Lee, So, Kyun Park, Moo, Mun, Seyoung, Koo, Ja-Won
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.05.2022
• Subjects: Animals; Chemokine CXCL10 - genetics; Cochlea; Cochlea - chemistry; Cochlea - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Endotoxemia - chemically induced; Endotoxemia - genetics; Female; Gene Expression Profiling - methods; Gene Expression Regulation - drug effects; Gene Regulatory Networks - drug effects; GTP-Binding Proteins - genetics; Injections, Intraperitoneal; Lipopolysaccharide; Lipopolysaccharides - adverse effects; Mice; Microarray; Oligonucleotide Array Sequence Analysis; Random Allocation; Transcriptome; Ubiquitin-Protein Ligases - genetics; Gabra; BBB; cxcl10; Transcriptome; PPI; Microarray; LPS; Grm1; rnf125; α-1acidglycoprotein; Stxbp1; IFN; DEGs; Il6; Camk2a; RT-PCR; Ccl5; Lipopolysaccharide; MF; Nos1; Cxcl1; Lbp; TLR; Grin1; ISG; MDS; Il-1β; GBPs; CC; BPs; Syt1; RMA; qRT-PCR; gbp2; Myd88; Dnm1; Rab3a; CT; Saa; Bcl3; Cochlea; GPCR; BLB; STRING; Tlr2
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2022.146347

•The condition of the LPS-induced endotoxemia elicits transcriptional alternations to the cochlea, but not histological damage.•Interferon- and chemotaxis-related genes were dose-dependently upregulated by LPS-induced endotoxemia.•Upregulated differentially expressed genes were associated with inflammation, positive regulation of immune responses, and regulation of cell adhesion.•Downregulated differentially expressed genes were associated with chemical synaptic transmission and the synaptic vesicle cycle.•These results provide an additional basis on the changes in the expression of genes in the cochlea in response to LPS-induced endotoxemia. Lipopolysaccharide (LPS)-induced endotoxemia alters intracochlear homeostasis and potentiates aminoglycoside-induced ototoxicity. However, the pathological mechanisms in the cochlea following systemic LPS-induced inflammation are unclear. In this study, three groups of mice received intraperitoneal injections [group A, saline control (n = 10); group B, 1 mg/kg LPS (n = 10); group C, 10 mg/kg LPS (n = 10)]. After 24 h, gene expression in cochlea samples was analyzed using DNA microarrays covering 28,853 genes in a duplicate manner. A total of 505 differentially expressed genes (DEGs) (≥2.0-fold change; p < 0.05) were identified. Interferon- and chemotaxis-related genes, including gbp2, gbp5, cxcl10, and Rnf125, were dose-dependently upregulated by LPS-induced endotoxemia. These results were verified by RT-qPCR. Upregulated DEGs were associated with inflammation, positive regulation of immune responses, and regulation of cell adhesion, while downregulated ones were associated with chemical synaptic transmission and the synaptic vesicle cycle. Protein-protein interaction included four functional clusters associated with interleukin-4, −10, and −13 and G protein-coupled receptor (GPCR) ligand binding; activation of matrix metalloproteinases and collagen degradation; recruitment of amyloid A proteins; and neutrophil degranulation. The findings of this study provide an additional basis on changes in the expression of genes in the cochlea in response to LPS-induced endotoxemia.