Abstract
Clostridium perfringens type C (C. perfringens type C) is one of the main microbial pathogens responsible for piglet diarrhea worldwide, causing substantial economic losses for pig-rearing industries. The mitogen-activated protein kinase (MAPK) signaling pathway is a key regulator of inflammatory bowel disease, especially necrotic enteritis. However, whether and how the MAPK signaling pathway is involved in regulating the process of piglet diarrhea when challenged by C. perfringens type C are still unknown. Here, we screened 38 differentially expressed genes (DEGs) in piglets' ileum tissues experimentally infected with C. perfringens type C that were enriched in the Sus scrofa MAPK signaling pathway, based on our previous transcriptome data. Of these DEGs, 12 genes (TRAF2, MAPK8, and GADD45G, among others) were upregulated whereas 26 genes (MAPK1, TP53, and CHUK, among others) were downregulated in the infected group. Our results showed that MAPK1, TP53, MAPK8, MYC, and CHUK were in the core nodes of the PPI network. Additionally, we obtained 35 lncRNAs from the sequencing data, which could be trans-targeted to MAPK signaling pathway genes and were differentially expressed in the ileum tissues infected with C. perfringens. We used qRT-PCR to verify the expression levels of genes and lncRNAs related to the MAPK signaling pathway; their expression patterns were consistent with RNA sequencing data. Our results provide strong support for deeply exploring the role of the MAPK signaling pathway in diarrhea caused by C. perfringens type C.
Highlights
Piglet diarrhea is one of the most severe diseases afflicting piglets, leading to their delayed growth and development, low feed returns, and even death, which has seriously damaged the economic development of pig industries globally [1]
The C. perfringens alpha toxin can induce the release of cytokine IL-8 by activating the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathways [9], while the C. perfringens beta toxin can cause the phosphorylation of p38 and Jun N-terminal kinases (JNKs) [10]
Based on the results of the KEGG analysis, we selected the first 14 types of significant enrichment pathways related to the immune system (Table S1-2), such as the MAPK signaling pathway, NF-kappa B signaling pathway, T cell receptor signaling pathway, nucleotidebinding oligomerization domain-containing protein- (NOD-) like receptor signaling pathway, retinoic acid-inducible gene 1 protein- (RIG-I-) like receptor signaling pathway, and toll-like receptor signaling pathway (Figure 1)
Summary
Piglet diarrhea is one of the most severe diseases afflicting piglets, leading to their delayed growth and development, low feed returns, and even death, which has seriously damaged the economic development of pig industries globally [1]. The Clostridium perfringens type C (C. perfringens type C) is a gas-tolerant bacterium widely distributed in nature that may cause various diseases in animals, including cellulitis, gas gangrene, intestinal toxemia, and necrotic enteritis [2, 3]. C. perfringens type C can produce alpha and beta toxins, which are known to play critical roles in intestinal epithelial cell damage and necrosis, as well as intestinal inflammatory responses [4, 5]. The mitogen-activated protein kinase (MAPK) signaling pathway is known to participate in various biological processes including innate immunity, cell growth, stress response, apoptosis, and differentiation [6]. The C. perfringens alpha toxin can induce the release of cytokine IL-8 by activating the ERK1/2 and p38 MAPK signaling pathways [9], while the C. perfringens beta toxin can cause the phosphorylation of p38 and JNK [10]. It has been reported that p38, JNK1/2, and BioMed Research International
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