dc.contributor.authorPhua, Terri
dc.contributor.authorSng, Ming Keat
dc.contributor.authorTan, Eddie Han Pin
dc.contributor.authorChee, Dickson Shao Liang
dc.contributor.authorLi, Yinliang
dc.contributor.authorWee, Jonathan Wei Kiat
dc.contributor.authorTeo, Ziqiang
dc.contributor.authorChan, Jeremy Soon Kiat
dc.contributor.authorLim, Maegan Miang Kee
dc.contributor.authorTan, Chek Kun
dc.contributor.authorZhu, Pengcheng
dc.contributor.authorArulampalam, Velmurugesan
dc.contributor.authorTan, Nguan Soon
dc.identifier.citationPhua, T., Sng, M. K., Tan, E. H. P., Chee, D. S. L., Li, Y., Wee, J. W. K., et al. (2017). Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin. Scientific Reports, 7, 44351-.en_US
dc.description.abstractMany gastrointestinal diseases exhibit a protracted and aggravated inflammatory response that can lead to hypercytokinaemia, culminating in extensive tissue damage. Recently, angiopoietin-like 4 (ANGPTL4) has been implicated in many inflammation-associated diseases. However, how ANGPTL4 regulates colonic inflammation remains unclear. Herein, we show that ANGPTL4 deficiency in mice (ANGPTL4−/−) exacerbated colonic inflammation induced by dextran sulfate sodium (DSS) or stearic acid. Microbiota was similar between the two genotypes prior DSS challenge. A microarray gene expression profile of the colon from DSS-treated ANGPTL4−/− mice was enriched for genes involved in leukocyte migration and infiltration, and showed a close association to inflamed ulcerative colitis (UC), whereas the profile from ANGPTL4+/+ littermates resembled that of non-inflamed UC biopsies. Bone marrow transplantation demonstrates the intrinsic role of colonic ANGPTL4 in regulating leukocyte infiltration during DSS-induced inflammation. Using immortalized human colon epithelial cells, we revealed that the ANGPTL4-mediated upregulation of tristetraprolin expression operates through CREB and NF-κB transcription factors, which in turn, regulates the stability of chemokines. Together, our findings suggest that ANGPTL4 protects against acute colonic inflammation and that its absence exacerbates the severity of inflammation. Our findings emphasize the importance of ANGPTL4 as a novel target for therapy in regulating and attenuating inflammation.en_US
dc.description.sponsorshipMOE (Min. of Education, S’pore)en_US
dc.format.extent16 p.en_US
dc.relation.ispartofseriesScientific Reportsen_US
dc.rights© 2017 The Author(s) (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAcute inflammationen_US
dc.titleAngiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolinen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.description.versionPublished versionen_US

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