Quercetin Increases MUC2 and MUC5AC Gene Expression and Secretion in Intestinal Goblet Cell-Like LS174T via PLC/PKCα/ERK1-2 Pathway

Abstract

The main dietary flavonoid quercetin, is known to preserve the integrity of gastrointestinal barrier and to have anti-inflammatory, anti-cancer, anti-fibrotic, and other beneficial properties. Many of the biological effects of quercetin appear to be associated to the modulation of cell signaling pathways, rather than to its antioxidant activity. In spite of the large number of data available on the molecular and cellular mechanisms by which quercetin exerts its biological effects, including protection of intestinal barrier function, there is a lack of data about the role of this substance on the expression and/or the secretion of mucins released by intestinal goblet cells. Here we investigated the effects of quercetin on the secretion and the gene expression of the main intestinal gel-forming mucins, MUC2 and MUC5AC, and the signaling mechanisms underlined, in human intestinal goblet cell-like LS174T. We found that quercetin increases intracellular Ca2+ levels and induces MUC2 and MUC5AC secretion in a Ca2+-dependent manner. Quercetin also induces mRNA levels of both secretory mucins. Quercetin stimulation of LS174T cells increases phosphorylation levels of extracellular signal regulated kinase (ERK)1-2 and protein kinase C (PKC) α and the induction of MUC2 and MUC5AC secretion and mRNA relies on phospholipase C (PLC), PKC, and ERK1-2 signaling pathways since the PLC inhibitor U73122, the PKC inhibitor bisindolylmaleimide (BIM) and the ERK1-2 pathway inhibitor PD98059, all revert the stimulatory effects of quercetin. We also demonstrated that the induction of mucin gene expression by quercetin is not limited to goblet cells. Indeed, quercetin induces mRNA levels of MUC2 and MUC5AC via PKCα/ERK1-2 pathway also in the human intestinal epithelial Caco-2 cells. These data highlight a novel mechanism thereby quercetin, regulating the secretory function of intestinal goblet cells and mucin levels in enterocytes may exert its protective effects on intestinal mucosal barrier.

Effects of dietary quercetin on the antioxidative status and cecal microbiota in broiler chickens fed with oxidized oil

“…Quercetin (800 ppm) significantly alleviated the downregulation of MUC2 mRNA expression induced by oxidized oil. In an in vitro experiment of LS174 T cells, a human intestinal goblet cell–like cell, quercetin could induce mRNA levels and secretion of MUC2 via the protein kinase C alpha/extracellular regulated protein kinases 1-2 pathway, and the same effects of quercetin also observed in the intestinal epithelial Caco-2 cells ( Damiano et al., 2018 ). As a member of leucine zipper transcription factors, Nrf2 was essential for the induction of many stress-responsive or cytoprotective enzymes, such as CAT, SOD, GPX, HO-1, TXN, and glutamate–cysteine ligase ( Surh et al., 2008 ).…”

Exogenous NAD+ Stimulates MUC2 Expression in LS 174T Goblet Cells via the PLC-Delta/PTGES/PKC-Delta/ERK/CREB Signaling Pathway

“…Similarly, CREB mediates MUC5AC overexpression induced by prostaglandin F 2α in airway epithelial cells through the PKC/ERK/p90 ribosomal protein kinase/CREB signaling cascade [26]. Quercetin increases MUC2 and MUC5AC gene expression and secretion via the PKCα/ERK1-2 pathway in LS 174T and Caco-2 cells [39]. Although we should measure the release of arachidonic acid upon NAD + treatment in the further study, in this study, exogenous NAD + showed the stimulating effect on MUC2 expression via involvement of PLC/PKC/MAPK pathway and CREB.…”

Intestine motility, secretion, and constipation treatment principles

“…В регуляции кишечной перистальтики и секреции заметную роль играют флавоноиды -полифенольные соединения, содержащиеся в большинстве продуктов растительного происхождения. Они стимулируют выработку муцина и энтерогормонов, а имеющие строение гликозидов, возможно, прямо влияют на гладкие миоциты [13].…”