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Title: STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis.
Austin Authors: Pang, Lokman;Huynh, Jennifer;Alorro, Mariah G;Li, Xia;Ernst, Matthias ;Chand, Ashwini L 
Affiliation: Department of Mathematics and Statistics, La Trobe University, Bundoora, VIC 3083, Australia
Olivia Newton-John Cancer Research Institute
La Trobe University School of Cancer Medicine, Heidelberg, VIC 3084, Australia
Issue Date: 12-Feb-2021 2021-02-12
Publication information: Biomedicines 2021; 9(2); 187
Abstract: The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.
DOI: 10.3390/biomedicines9020187
ORCID: 0000-0001-7134-989X
Journal: Biomedicines
PubMed URL: 33673239
ISSN: 2227-9059
Type: Journal Article
Subjects: IL-6ST/gp130
intestinal barrier function
Appears in Collections:Journal articles

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