Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/83483
Title: Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin
Authors: Phua, Terri
Sng, Ming Keat
Tan, Eddie Han Pin
Chee, Dickson Shao Liang
Li, Yinliang
Wee, Jonathan Wei Kiat
Teo, Ziqiang
Chan, Jeremy Soon Kiat
Lim, Maegan Miang Kee
Tan, Chek Kun
Zhu, Pengcheng
Arulampalam, Velmurugesan
Tan, Nguan Soon
Keywords: Acute inflammation
Physiology
Issue Date: 2017
Source: Phua, 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-.
Series/Report no.: Scientific Reports
Abstract: Many 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.
URI: https://hdl.handle.net/10356/83483
http://hdl.handle.net/10220/42647
ISSN: 2045-2322
DOI: 10.1038/srep44351
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/
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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