The Role of -Goblet Cell Interactions in Melatonin-Mediated Improvements in Sleep Deprivation-Induced Colitis

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2022 Mar 31

PMID 35355860

Authors

Ting Gao

Zixu Wang

Jing Cao

Yulan Dong

Yaoxing Chen

Affiliations

Soon will be listed here.

Abstract

Background: Our previous studies demonstrated that melatonin could effectively ameliorate sleep deprivation- (SD-) caused oxidative stress-mediated gut microbiota disorder and colitis. The research further clarified the mechanism of melatonin in improving colitis from the perspective of the interaction between and goblet cells.

Methods: A seventy-two hours SD mouse model with or without melatonin intervention and fecal microbiota transplantation (FMT) to explore the vital position of -goblet cell interactions in melatonin improving SD-induced colitis. Moreover, or LPS-supplied mice were assessed, and the influence of melatonin on -goblet cell interactions-mediated oxidative stress caused colitis. Furthermore, in vitro experiment investigated the regulation mechanism of melatonin.

Results: Our study showed that SD induced colitis, with upregulation of and LPS levels and reductions in goblet cells number and MUC2 protein. Similarly, FMT from SD mice, veronii colonization, and LPS treatment restored the SD-like goblet cells number and MUC2 protein decrease and colitis. Moreover, LPS treatment downregulated the colonic antioxidant capacity. Yet, melatonin intervention reversed all consequence in SD, veronii colonization, and LPS-treated mice. In vitro, melatonin reversed veronii- or LPS-induced MUC2 depletion in mucus-secreting human HT-29 cells via increasing the expression level of Villin, Tff3, p-GSK-3, -catenin, and melatonin receptor 2 (MT2) and decreasing the level of p-IB, p-P65, ROS, TLR4, and MyD88 proteins, while the improvement effect was blocked with pretreatment with a MT2 antagonist but were mimicked by TLR4 and GSK-3 antagonists and ROS scavengers.

Conclusions: Our results demonstrated that melatonin-mediated MT2 inhibits -goblet cell interactions to restore the level of MUC2 production via LPS/TLR4/MyD88/GSK-3/ROS/NF-B loop, further improving colitis in SD mice.

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