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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 2/2016

01-02-2016 | Original Article

A Role for MYC in Lithium-Stimulated Repair of the Colonic Epithelium After DSS-Induced Damage in Mice

Authors: Wesley M. Raup-Konsavage, Timothy K. Cooper, Gregory S. Yochum

Published in: Digestive Diseases and Sciences | Issue 2/2016

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Abstract

Background

Chronic inflammation disrupts the colonic epithelial layer in patients afflicted by ulcerative colitis (UC). The use of inhibitors of glycogen synthase kinase three beta (GSK3β) has proven efficacious to mitigate disease symptoms in rodent models of UC by reducing the pro-inflammatory response. Less is known about whether these inhibitors promote colonic regeneration by stimulating proliferation of colonic epithelial cells.

Aims

We investigated whether delivery of the GSK3β inhibitor, lithium chloride (LiCl), during the recovery period from acute DSS-induced colitis in mice promoted colonic regeneration and ameliorated disease symptoms. We also tested whether the c-MYC transcription factor (MYC) was involved in this response.

Methods

Acute colitis was induced by administration of 2.5 % dextran sodium sulfate (DSS) to wild-type C57BL/6 mice for 5 days. During the recovery period, mice received a daily intraperitoneal (IP) injection of LiCl or 1X PBS as a control. Mice were weighed, colon lengths measured, disease activity index (DAI) scores were assessed, and histological analyses were performed on colonic sections. We analyzed transcripts and proteins in purified preparations of the colonic epithelium. We delivered the MYC inhibitor 10058-F4 via IP injection to assess the role of MYC in colonic regeneration.

Results

Lithium treatments promoted recovery from acute DSS-induced damage by increasing expression of Myc transcripts, MYC proteins, and expression of a subset of Wnt/MYC target genes in the colonic epithelium. Inhibiting MYC function with 10058-F4 blunted the lithium response.

Conclusions

By inducing Myc expression in the colonic epithelium, lithium promotes colonic regeneration after DSS-induced colitis. Therefore, the use of lithium may be of therapeutic value to manage individuals afflicted by UC.
Appendix
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Metadata
Title
A Role for MYC in Lithium-Stimulated Repair of the Colonic Epithelium After DSS-Induced Damage in Mice
Authors
Wesley M. Raup-Konsavage
Timothy K. Cooper
Gregory S. Yochum
Publication date
01-02-2016
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 2/2016
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3852-0

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