Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin
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 co...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2017
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/83483 http://hdl.handle.net/10220/42647 |
| _version_ | 1811686747449327616 |
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| author | 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 |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences 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 |
| author_sort | Phua, Terri |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T05:05:20Z |
| format | Journal Article |
| id | ntu-10356/83483 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:05:20Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/834832023-02-28T16:58:23Z Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin 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 School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Acute inflammation Physiology 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. MOE (Min. of Education, S’pore) Published version 2017-06-09T08:11:40Z 2019-12-06T15:23:58Z 2017-06-09T08:11:40Z 2019-12-06T15:23:58Z 2017 Journal Article 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-. 2045-2322 https://hdl.handle.net/10356/83483 http://hdl.handle.net/10220/42647 10.1038/srep44351 en Scientific Reports © 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/ 16 p. application/pdf |
| spellingShingle | Acute inflammation Physiology 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 Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin |
| title | Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin |
| title_full | Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin |
| title_fullStr | Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin |
| title_full_unstemmed | Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin |
| title_short | Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin |
| title_sort | angiopoietin like 4 mediates colonic inflammation by regulating chemokine transcript stability via tristetraprolin |
| topic | Acute inflammation Physiology |
| url | https://hdl.handle.net/10356/83483 http://hdl.handle.net/10220/42647 |
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