Exogenous NAD+ induces mucin secretion in LS 174T goblet cells via the PLC-delta/PTGES/PKC-delta/ERK1/2/CREB signalling pathway
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ABSTRACT:
PROVIDER: PRJNA588296 | ENA |
REPOSITORIES: ENA
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Project description:Mucin, one of family of glycoprotein that is a major component of the mucus layer in the intestine, is associated with antimicrobial activity and gut immune system function. Currently, mucin is mainly known for its critical function in defence against toxic molecules and pathogens. In this study, we investigated the stimulatory effects of exogenous nicotinamide adenine dinucleotide (NAD+) on the expression of MUC2, the main mucin subtype in the intestine, in LS 174T goblet cells. NAD+ significantly stimulated MUC2 expression at the transcriptional and translational levels. Through RNA sequencing, we found that the expression of genes involved in arachidonic acid metabolism was increased in NAD+-treated cells compared with the negative control cells. For example, NAD+ treatment increased phospholipase C (PLC)-δ and prostaglandin E synthase (PTGES) expression, which was inhibited by the appropriate inhibitors. Among the protein kinase C (PKC) isozymes, PKC-δ was involved in the increase in MUC2 expression. In addition, extracellular signal-regulated kinase (ERK)1/2 and cyclic AMP (cAMP) response element-binding protein (CREB) transcript levels were higher in NAD+-treated cells than in the negative control cells, and the enhanced levels of phosphorylated CREB augmented MUC2 expression. In conclusion, exogenous NAD+ increases MUC2 expression by stimulating the PLC-δ/PTGES/PKC-δ/ERK1/2/CREB signalling pathway.
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