Transcriptomic and Bioinformatic Analyses Identifying a Central Mif-Cop9-Nf-kB Signaling Network in Innate Immunity Response of Ciona robusta

• Published in: International journal of molecular sciences Vol. 24; no. 4; p. 4112
• Main Authors: La Paglia, Laura, Vazzana, Mirella, Mauro, Manuela, Dumas, Francesca, Fiannaca, Antonino, Urso, Alfonso, Arizza, Vincenzo, Vizzini, Aiti
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18-02-2023; MDPI
• Subjects: Bioinformatics; Cell cycle; Cell differentiation; Ciona robusta; cytokine; Cytokines; DNA repair; Gene expression; Genes; Hemocytes; Inflammation; Inflammatory response; Innate immunity; Intracellular signalling; Invertebrates; Kinases; Leukocytes (granulocytic); Lipopolysaccharides; LPS; Macrophages; MicroRNAs; miRNA; Next-generation sequencing; NF-κB protein; Pharynx; Photomorphogenesis; Phylogenetics; Phylogeny; Polymerase chain reaction; Proteasomes; Proteins; Signal transduction; transcriptome; Transcriptomes; Transcriptomics; Vertebrates; cytokine; miRNA; Ciona robusta; innate immunity; transcriptome; LPS
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24044112

The Ascidian
is a powerful model for studying innate immunity. LPS induction activates inflammatory-like reactions in the pharynx and the expression of several innate immune genes in granulocyte hemocytes such as cytokines, for instance, macrophage migration inhibitory factors (CrMifs). This leads to intracellular signaling involving the Nf-kB signaling cascade that triggers downstream pro-inflammatory gene expression. In mammals, the COP9 (Constitutive photomorphogenesis 9) signalosome (CSN) complex also results in the activation of the NF-kB pathway. It is a highly conserved complex in vertebrates, mainly engaged in proteasome degradation which is essential for maintaining processes such as cell cycle, DNA repair, and differentiation. In the present study, we used bioinformatics and in-silico analyses combined with an in-vivo LPS exposure strategy, next-generation sequencing (NGS), and qRT-PCR to elucidate molecules and the temporal dynamics of Mif cytokines, Csn signaling components, and the Nf-κB signaling pathway in
. A qRT-PCR analysis of immune genes selected from transcriptome data revealed a biphasic activation of the inflammatory response. A phylogenetic and STRING analysis indicated an evolutionarily conserved functional link between the Mif-Csn-Nf-kB axis in ascidian
during LPS-mediated inflammation response, finely regulated by non-coding molecules such as microRNAs (miRNAs).