-
Cells May 2024() has a potential zoonotic risk, with a high proportion of co-infection occurring with () and other diarrheal pathogens. Despite its high prevalence, the cellular...
NLRX1 Mediates the Disruption of Intestinal Mucosal Function Caused by Porcine Astrovirus Infection via the Extracellular Regulated Protein Kinases/Myosin Light-Chain Kinase (ERK/MLCK) Pathway.
() has a potential zoonotic risk, with a high proportion of co-infection occurring with () and other diarrheal pathogens. Despite its high prevalence, the cellular mechanism of pathogenesis is ill-defined. Previous proteomics analyses have revealed that the differentially expressed protein NOD-like receptor X1 (NLRX1) located in the mitochondria participates in several important antiviral signaling pathways in infection, which are closely related to mitophagy. In this study, we confirmed that infection significantly up-regulated NLRX1 and mitophagy in Caco-2 cells, while the silencing of NLRX1 or the treatment of mitophagy inhibitor 3-MA inhibited PAstV-4 replication. Additionally, infection triggered the activation of the extracellular regulated protein kinases/ myosin light-chain kinase (ERK/MLCK) pathway, followed by the down-regulation of tight-junction proteins (occludin and ZO-1) as well as MUC-2 expression. The silencing of NLRX1 or the treatment of 3-MA inhibited myosin light-chain (MLC) phosphorylation and up-regulated occludin and ZO-1 proteins. Treatment of the ERK inhibitor PD98059 also inhibited MLC phosphorylation, while MLCK inhibitor ML-7 mitigated the down-regulation of mucosa-related protein expression induced by infection. Yet, adding PD98059 or ML-7 did not affect NLRX1 expression. In summary, this study preliminarily explains that NLRX1 plays an important role in the disruption of intestinal mucosal function triggered by infection via the ERK/MLC pathway. It will be helpful for further antiviral drug target screening and disease therapy.
Topics: Animals; Intestinal Mucosa; Caco-2 Cells; Humans; Swine; Myosin-Light-Chain Kinase; Extracellular Signal-Regulated MAP Kinases; Astroviridae Infections; Mamastrovirus; Mitochondrial Proteins; MAP Kinase Signaling System; Swine Diseases; Signal Transduction
PubMed: 38891045
DOI: 10.3390/cells13110913