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High MUC2 production in goblet cells causes increased susceptibility to ER stress and apoptosis (151.4)
Author(s) -
Tawiah Adelaide,
Moreau France,
Chadee Kris
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.151.4
Subject(s) - unfolded protein response , mucin 2 , tunicamycin , apoptosis , goblet cell , mucin , endoplasmic reticulum , mg132 , chemistry , microbiology and biotechnology , secretion , cancer research , biology , proteasome inhibitor , endocrinology , epithelium , biochemistry , gene expression , genetics , gene
MUC2, a large glycoprotein produced by goblet cells in the colon, forms a protective mucus blanket over the epithelium as the first line of host defense. During pathological conditions such as inflammatory bowel diseases, there is accelerated biosynthesis and secretion of MUC2. Surprisingly, little information is known on how MUC2 production is regulated and whether goblet cells undergo increased stress in response to high MUC2 biosynthesis and secretion. In this study we investigated the role of MUC2 in goblet cell stress using a high mucin producing cell line, HT29‐H, and a clone of HT29‐H (HT29‐L) in which MUC2 has been silenced using lentivirus shRNA. Cells were treated with tunicamycin and MG132, and markers for endoplasmic reticulum (ER) stress and apoptosis were quantified. Compared to HT29‐L cells, HT29‐H cells exhibited a greater dose‐and time‐dependent increase in ER stress markers GRP78, ATF4, CHOP, sXBP1 and AGR2 in response to both tunicamycin and MG132. ER stress also caused a decrease in phosphorylation of Akt and increased apoptosis in HT29‐H cells 6h after treatment. Phospho‐Akt in HT29‐L cells was however sustained, decreasing slightly only after 24h with less apoptosis compared to HT29‐H cells. Our findings indicate that MUC2 induces goblet cell stress and apoptosis which could subsequently lead to diminished mucus barrier function. Grant Funding Source : Supported by CIHR