Lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets
Improving the long-term prognosis of ulcerative colitis (UC) requires sustained deep mucosal colonic healing with histologic remission, making the study of colonic tissue regeneration essential. In experimental colitis models, lipid metabolites are recognized as pivotal components of this process. T...
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| Format: | Journal Article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10356/160159 |
| _version_ | 1826125282817343488 |
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| author | Bjerrum, Jacob Tveiten Wang, Yulan Zhang, Jingtao Riis, Lene Buhl Nielsen, Ole Haagen Seidelin, Jakob Benedict |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Bjerrum, Jacob Tveiten Wang, Yulan Zhang, Jingtao Riis, Lene Buhl Nielsen, Ole Haagen Seidelin, Jakob Benedict |
| author_sort | Bjerrum, Jacob Tveiten |
| collection | NTU |
| description | Improving the long-term prognosis of ulcerative colitis (UC) requires sustained deep mucosal colonic healing with histologic remission, making the study of colonic tissue regeneration essential. In experimental colitis models, lipid metabolites are recognized as pivotal components of this process. This study aimed to describe the kinetics of wound healing and lipid metabolites engaged in regeneration in the normal colonic mucosa and how they are affected in UC to reveal new therapeutic targets. Experimental colonic wounds were created endoscopically in quiescent UC (n=21) and controls (n=9), and the healing process was surveilled by serial endoscopies and cross-sectional wound biopsies post-wounding. Biopsies were analyzed by liquid chromatography coupled with mass spectrometry. Endoscopic wound scores were significantly higher in UC at day two (p=0.001) and seven (p<0.0001) post-wounding, demonstrating a prolonged wound healing process. The wound scores were correlated with lipid mediators crucial for normal regeneration and sustained UC-specific changes in key phospholipids and eicosanoids, i.e., lysophosphatidylcholine, phosphatidylcholine, lysophosphatidic acid, phosphatidylglycerol, phosphatidylinositol, prostaglandin D2, and prostaglandin E1, were observed. A prolonged wound healing process is identified in quiescent UC with altered disease specific lipidomic trajectories providing potential novel therapeutic avenues for stimulating mucosal regeneration as an add-on to the traditional immune suppression treatment. |
| first_indexed | 2024-10-01T06:34:06Z |
| format | Journal Article |
| id | ntu-10356/160159 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:34:06Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1601592023-03-05T16:52:32Z Lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets Bjerrum, Jacob Tveiten Wang, Yulan Zhang, Jingtao Riis, Lene Buhl Nielsen, Ole Haagen Seidelin, Jakob Benedict Lee Kong Chian School of Medicine (LKCMedicine) Singapore Phenome Centre Science::Medicine Eicosanoids Inflammatory Bowel Disease Improving the long-term prognosis of ulcerative colitis (UC) requires sustained deep mucosal colonic healing with histologic remission, making the study of colonic tissue regeneration essential. In experimental colitis models, lipid metabolites are recognized as pivotal components of this process. This study aimed to describe the kinetics of wound healing and lipid metabolites engaged in regeneration in the normal colonic mucosa and how they are affected in UC to reveal new therapeutic targets. Experimental colonic wounds were created endoscopically in quiescent UC (n=21) and controls (n=9), and the healing process was surveilled by serial endoscopies and cross-sectional wound biopsies post-wounding. Biopsies were analyzed by liquid chromatography coupled with mass spectrometry. Endoscopic wound scores were significantly higher in UC at day two (p=0.001) and seven (p<0.0001) post-wounding, demonstrating a prolonged wound healing process. The wound scores were correlated with lipid mediators crucial for normal regeneration and sustained UC-specific changes in key phospholipids and eicosanoids, i.e., lysophosphatidylcholine, phosphatidylcholine, lysophosphatidic acid, phosphatidylglycerol, phosphatidylinositol, prostaglandin D2, and prostaglandin E1, were observed. A prolonged wound healing process is identified in quiescent UC with altered disease specific lipidomic trajectories providing potential novel therapeutic avenues for stimulating mucosal regeneration as an add-on to the traditional immune suppression treatment. Published version This study received financial support from Aase og Ejnar Danielsens Fond, Civilingeniør Frode V. Nygaard og Hustrus Fond, Aage og Johanne Louis-Hansens Fond, Colitis-Crohn Foreningen, and Frimodt-Heineke Fonden. 2022-07-14T01:39:58Z 2022-07-14T01:39:58Z 2022 Journal Article Bjerrum, J. T., Wang, Y., Zhang, J., Riis, L. B., Nielsen, O. H. & Seidelin, J. B. (2022). Lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets. International Journal of Biological Sciences, 18(5), 1813-1828. https://dx.doi.org/10.7150/ijbs.67112 1449-2288 https://hdl.handle.net/10356/160159 10.7150/ijbs.67112 35342362 2-s2.0-85127220635 5 18 1813 1828 en International Journal of Biological Sciences © 2022 The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. application/pdf |
| spellingShingle | Science::Medicine Eicosanoids Inflammatory Bowel Disease Bjerrum, Jacob Tveiten Wang, Yulan Zhang, Jingtao Riis, Lene Buhl Nielsen, Ole Haagen Seidelin, Jakob Benedict Lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets |
| title | Lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets |
| title_full | Lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets |
| title_fullStr | Lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets |
| title_full_unstemmed | Lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets |
| title_short | Lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets |
| title_sort | lipidomic trajectories characterize delayed mucosal wound healing in quiescent ulcerative colitis and identify potential novel therapeutic targets |
| topic | Science::Medicine Eicosanoids Inflammatory Bowel Disease |
| url | https://hdl.handle.net/10356/160159 |
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