Identification and Characterization of MAPK Signaling Pathway Genes and Associated lncRNAs in the Ileum of Piglets Infected by Clostridium perfringens Type C

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.

Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain

“…Previous studies, outside of the brain, have identified expression networks containing MAPK-pathway signaling genes and correlated lncRNAs [ 32 , 33 , 34 ]. Given that the expression of most lncRNA is highly tissue-specific, [ 35 ] characterizing the activity-driven lncRNA-MAPK interactome in the human brain, as we have done in this study, is a major step in identifying novel regulatory networks involving brain-specific lncRNA.…”

Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain

“…Previous studies, outside of the brain, have identified expression networks containing MAPK-pathway signaling genes and correlated lncRNAs [ 32 , 33 , 34 ]. Given that the expression of most lncRNA is highly tissue-specific, [ 35 ] characterizing the activity-driven lncRNA-MAPK interactome in the human brain, as we have done in this study, is a major step in identifying novel regulatory networks involving brain-specific lncRNA.…”

Potential pharmacological mechanisms of four active compounds of Macleaya cordata extract against enteritis based on network pharmacology and molecular docking technology

“…This activity induces the activation of caspase-1 and the maturation and secretion of the downstream pro-inflammatory factors IL-1β and IL-18 ( Sarvestani and McAuley, 2017 ; Li et al, 2019 ). MAPK1 is a significant MAPK signaling pathway component of the MAPK signaling pathway ( Luo et al, 2020 ). This target component can regulate a variety of cellular physiological and pathological functions, such as cell growth, adhesion, and differentiation through transcription, translation, and cytoskeleton rearrangement, and it is a key signaling molecule in the treatment of inflammation-related diseases ( Dong et al, 2021 ).…”

“…These results suggest that the PI3K-Akt signaling pathway plays a regulatory role in enteritis, which is consistent with our network pharmacological prediction. The MAPK signaling pathway is involved in various biological processes such as immunity, stress, cell growth, apoptosis, and differentiation, and it plays a key role in the release of pro-inflammatory cytokines ( Luo et al, 2020 ; Afroz et al, 2021 ). The MAPK family includes three subfamilies, namely, ERK, JNK, and p38 MAPK, which are associated with intestinal mucosal injury and are activated in inflammatory bowel disease to induce the release of cytokines such as IL-8 ( Luo et al, 2020 ).…”

“…The MAPK signaling pathway is involved in various biological processes such as immunity, stress, cell growth, apoptosis, and differentiation, and it plays a key role in the release of pro-inflammatory cytokines ( Luo et al, 2020 ; Afroz et al, 2021 ). The MAPK family includes three subfamilies, namely, ERK, JNK, and p38 MAPK, which are associated with intestinal mucosal injury and are activated in inflammatory bowel disease to induce the release of cytokines such as IL-8 ( Luo et al, 2020 ). Dong et al (2020a) reported that Astragalus polysaccharide could alleviate lipopolysaccharide (LPS)-induced intestinal inflammation via the MAPK signaling pathway.…”

FTO Regulates Apoptosis in CPB2-Treated IPEC-J2 Cells by Targeting Caspase 3 Apoptotic Protein

“…The influence of m6A-mediated RNA methylation on the development of CPTCIPD was investigated by treating IPEC-J2 cells with the CPB2 toxin (20 µg/mL) to construct an in vitro model of diarrhea in piglets [10,39]. The overall m6A methylation content was found to be elevated, while the expression of FTO was significantly reduced in the treated cells.…”

Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain

“…Previous studies, outside of the brain, have identified expression networks containing MAPK-pathway signaling genes and correlated lncRNAs [ 32 , 33 , 34 ]. Given that the expression of most lncRNA is highly tissue-specific, [ 35 ] characterizing the activity-driven lncRNA-MAPK interactome in the human brain, as we have done in this study, is a major step in identifying novel regulatory networks involving brain-specific lncRNA.…”

Potential pharmacological mechanisms of four active compounds of Macleaya cordata extract against enteritis based on network pharmacology and molecular docking technology

“…This activity induces the activation of caspase-1 and the maturation and secretion of the downstream pro-inflammatory factors IL-1β and IL-18 ( Sarvestani and McAuley, 2017 ; Li et al, 2019 ). MAPK1 is a significant MAPK signaling pathway component of the MAPK signaling pathway ( Luo et al, 2020 ). This target component can regulate a variety of cellular physiological and pathological functions, such as cell growth, adhesion, and differentiation through transcription, translation, and cytoskeleton rearrangement, and it is a key signaling molecule in the treatment of inflammation-related diseases ( Dong et al, 2021 ).…”

“…These results suggest that the PI3K-Akt signaling pathway plays a regulatory role in enteritis, which is consistent with our network pharmacological prediction. The MAPK signaling pathway is involved in various biological processes such as immunity, stress, cell growth, apoptosis, and differentiation, and it plays a key role in the release of pro-inflammatory cytokines ( Luo et al, 2020 ; Afroz et al, 2021 ). The MAPK family includes three subfamilies, namely, ERK, JNK, and p38 MAPK, which are associated with intestinal mucosal injury and are activated in inflammatory bowel disease to induce the release of cytokines such as IL-8 ( Luo et al, 2020 ).…”

“…The MAPK signaling pathway is involved in various biological processes such as immunity, stress, cell growth, apoptosis, and differentiation, and it plays a key role in the release of pro-inflammatory cytokines ( Luo et al, 2020 ; Afroz et al, 2021 ). The MAPK family includes three subfamilies, namely, ERK, JNK, and p38 MAPK, which are associated with intestinal mucosal injury and are activated in inflammatory bowel disease to induce the release of cytokines such as IL-8 ( Luo et al, 2020 ). Dong et al (2020a) reported that Astragalus polysaccharide could alleviate lipopolysaccharide (LPS)-induced intestinal inflammation via the MAPK signaling pathway.…”

FTO Regulates Apoptosis in CPB2-Treated IPEC-J2 Cells by Targeting Caspase 3 Apoptotic Protein

“…The influence of m6A-mediated RNA methylation on the development of CPTCIPD was investigated by treating IPEC-J2 cells with the CPB2 toxin (20 µg/mL) to construct an in vitro model of diarrhea in piglets [10,39]. The overall m6A methylation content was found to be elevated, while the expression of FTO was significantly reduced in the treated cells.…”

Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain

“…Previous studies, outside of the brain, have identified expression networks containing MAPK-pathway signaling genes and correlated lncRNAs [ 32 , 33 , 34 ]. Given that the expression of most lncRNA is highly tissue-specific, [ 35 ] characterizing the activity-driven lncRNA-MAPK interactome in the human brain, as we have done in this study, is a major step in identifying novel regulatory networks involving brain-specific lncRNA.…”

Potential pharmacological mechanisms of four active compounds of Macleaya cordata extract against enteritis based on network pharmacology and molecular docking technology

“…This activity induces the activation of caspase-1 and the maturation and secretion of the downstream pro-inflammatory factors IL-1β and IL-18 ( Sarvestani and McAuley, 2017 ; Li et al, 2019 ). MAPK1 is a significant MAPK signaling pathway component of the MAPK signaling pathway ( Luo et al, 2020 ). This target component can regulate a variety of cellular physiological and pathological functions, such as cell growth, adhesion, and differentiation through transcription, translation, and cytoskeleton rearrangement, and it is a key signaling molecule in the treatment of inflammation-related diseases ( Dong et al, 2021 ).…”

“…These results suggest that the PI3K-Akt signaling pathway plays a regulatory role in enteritis, which is consistent with our network pharmacological prediction. The MAPK signaling pathway is involved in various biological processes such as immunity, stress, cell growth, apoptosis, and differentiation, and it plays a key role in the release of pro-inflammatory cytokines ( Luo et al, 2020 ; Afroz et al, 2021 ). The MAPK family includes three subfamilies, namely, ERK, JNK, and p38 MAPK, which are associated with intestinal mucosal injury and are activated in inflammatory bowel disease to induce the release of cytokines such as IL-8 ( Luo et al, 2020 ).…”

“…The MAPK signaling pathway is involved in various biological processes such as immunity, stress, cell growth, apoptosis, and differentiation, and it plays a key role in the release of pro-inflammatory cytokines ( Luo et al, 2020 ; Afroz et al, 2021 ). The MAPK family includes three subfamilies, namely, ERK, JNK, and p38 MAPK, which are associated with intestinal mucosal injury and are activated in inflammatory bowel disease to induce the release of cytokines such as IL-8 ( Luo et al, 2020 ). Dong et al (2020a) reported that Astragalus polysaccharide could alleviate lipopolysaccharide (LPS)-induced intestinal inflammation via the MAPK signaling pathway.…”

FTO Regulates Apoptosis in CPB2-Treated IPEC-J2 Cells by Targeting Caspase 3 Apoptotic Protein

“…The influence of m6A-mediated RNA methylation on the development of CPTCIPD was investigated by treating IPEC-J2 cells with the CPB2 toxin (20 µg/mL) to construct an in vitro model of diarrhea in piglets [10,39]. The overall m6A methylation content was found to be elevated, while the expression of FTO was significantly reduced in the treated cells.…”