Korean J Physiol Pharmacol.  2019 Sep;23(5):367-379. 10.4196/kjpp.2019.23.5.367.

Profiling of remote skeletal muscle gene changes resulting from stimulation of atopic dermatitis disease in NC/Nga mouse model

• Lee D
• Seo Y
• Kim YW
• Kim S
• Choi J
• Moon SH
• Bae H
• Kim HS
• Kim H
• Kim JH
• Kim TY
• Kim E
• Yim S
• Lim I
• Bang H
• Kim JH
• Ko JH

• KMID: 2455813
• DOI: http://doi.org/10.4196/kjpp.2019.23.5.367

Abstract

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.

Keyword

Cytokines; Dermatitis, atopic; Microarray analysis; Mitochondria

MeSH Terms

Animals
Biomarkers
Calcium
Calcium Signaling
Citric Acid
Citric Acid Cycle
Cytokines
Dermatitis, Atopic*
Gene Ontology
Genome
Metabolism
Mice*
Microarray Analysis
Mitochondria
Muscle Cells
Muscle Contraction
Muscle, Skeletal*
Myoblasts
Myocardium
Oxidation-Reduction
Protein Interaction Maps
Pyroglyphidae
Receptors, Antigen, T-Cell
Skin
Biomarkers
Calcium
Citric Acid
Cytokines
Receptors, Antigen, T-Cell

Figure

• 

  Fig. 1 Regulated probes through house dust mite-induced atopic dermatitis (AD)-like in microarray analysis by fold change (FC) and p-value. (A) Up- and downregulated probes count compared between the AD-like (Itch) group and non-treated (NT) group (|FC| < 2). (B) Significantly regulated probes count compared between the Itch group and NT group (|FC| < 1.5 and 2 with p-value < 0.05).

• 

  Fig. 2 The top 20 most significantly stimulated pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis by house dust mite-induced atopy dermatitis-like. The p-value is expressed in log format. NF, nuclear factor; PI3K, phosphoinositide-3-kinase; HTLV-I, human T-cell lymphotropic virus type I; NOD, nucleotide-binding oligomerization domain; Jak-STAT, Janus kinase-signal transducers and activators of transcription.

• 

  Fig. 3 Analysis of differently expressed genes (DEGs) in Gene Ontology (GO) terms. The Top 10 GO terms and DEGs counts ordered by p-value were categorized in GO functional analysis sorted by biological process (A), cellular component (B), and molecular component (C). ***p < 0.001.

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