Screening of genes associated with inflammatory responses in the endolymphatic sac reveals underlying mechanisms for autoimmune inner ear diseases

Abstract

The current study analyzed gene expression profiles of the endolymphatic sac (ES) in rats and identified expressed genes, present in the human and rat ES, to reveal key hubs for inflammatory responses. Microarray data (accession no. E-MEXP-3022) were obtained from the European Bioinformatics Institute database, including three biological replicates of ES plus dura tissues and three replicates of pure dura tissues form rats. Differentially expressed genes (DEGs) were screened using the Linear Model for Microarray data method and a protein-protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes/Proteins database followed by a module analysis via Clustering with Overlapping Neighborhood Expansion. Function enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery online tool. A total of 612 DEGs were identified, including 396 upregulated and 216 downregulated genes. Gene ontology term enrichment analysis indicated DEGs were associated with cell adhesion, including α5-integrin (Itga1) and secreted phosphoprotein 1 (Spp1); T cell co-stimulation, including C-C chemokine ligand (Ccl)21 and Ccl19; and the toll-like receptor signaling pathway, including toll-like receptor (Tlr)2, Tlr7 and Tlr8. These conclusions were supported by Kyoto Encyclopedia of Genes and Genomes pathway analyses revealing extracellular matrix-receptor interaction, including Itga1 and Spp1; leukocyte transendothelial migration, includingclaudin-4 (Cldn4); and malaria, including Tlr2. The hub roles of Itga1, Cd24 and Spp1 were revealed by calculating three topological properties of the PPI network. Ccl21, Ccl19 and Cldn4 were demonstrated to be crucial following significant module analysis according to the corresponding threshold, which revealed they were enriched in inflammation pathways. Tlr7, Tlr2, granzyme m and Tlr8 were common genes associated with inflammatory responses in rat and human ES. In conclusion, abnormal expression of the aforementioned inflammation-associated genes may be associated with the development of autoimmune inner ear diseases.

GRAIL gene knockout mice protect against aging-related and noise-induced hearing loss

“…CCL21 and CCL19 are genes encoding the pro-inflammatory chemokine ligands that play an essential role in recruiting normal lymphocyte or activated T cells from the peripheral blood to the local injured area in traumatic and acute noise stresses. 28 IL25 is a pro-inflammatory cytokine favoring the Th2-type immune response. 29 SAA1 is a major acute-phase protein that is triggered by an inflammation response associated with the stimulation of cytokine/chemokine, including IL8, IL6, CXCL5, and CCL2 production and knockdown of SAA1 , resulting in a significant reduction of the pro-inflammatory cytokines and chemokines.…”

TMT-Based Quantitative Proteomics Reveals Cochlear Protein Profile Alterations in Mice with Noise-Induced Hearing Loss

“…ITGA1 was also reported to be closely associated with diabetes and diabetic retinopathy [ 34 , 36 ]. A previous study has revealed that abnormal expression of ITGA1, which was an inflammatory-associated gene, may be associated with the development of autoimmune inner ear disease [ 37 ]. In this study, ITGA1 was found to be significantly upregulated in the noise-stimulated mice cochlea.…”

A Proteomic View of the Cross-Talk Between Early Intestinal Microbiota and Poultry Immune System

“…Indeed, high expression of MYL9/12 was related to sepsis-induced acute kidney injury, inflamed mouse airways, and patients with eosinophilic chronic rhinosinusitis (Wu et al, 2015;Hayashizaki et al, 2016). Similarly, Zhang et al (2018) identified ITGA1 as an inflammatory-associated gene. Notably, we speculate that the high SFB population may be driving the predicted ileal mucosa proinflammatory status found in broilers early exposed to L. Nevertheless, the mechanism underlying SFB-mediated inflammation is yet unknown and must be further explored.…”