ID 112391
Author
Murase, Remi The University of Tokyo|Tokyo Metropolitan Institute of Medical Science
Taketomi, Yoshitaka The University of Tokyo|Tokyo Metropolitan Institute of Medical Science
Miki, Yoshimi The University of Tokyo|Tokyo Metropolitan Institute of Medical Science
Nishito, Yasumasa Tokyo Metropolitan Institute of Medical Science
Saito, Moe Tokyo Metropolitan Institute of Medical Science|Tokyo University of Pharmacy and Life Science
Fukami, Kiyoko Tokyo University of Pharmacy and Life Science
Yamamoto, Kei Tokyo Metropolitan Institute of Medical Science|Tokushima University|Japan Agency for Medical Research and Development Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Murakami, Makoto The University of Tokyo|Tokyo Metropolitan Institute of Medical Science|Japan Agency for Medical Research and Development
Content Type
Journal Article
Description
Lipid mediators play pivotal roles in colorectal cancer and colitis, but only a limited member of the phospholipase A2 (PLA2) subtypes, which lie upstream of various lipid mediators, have been implicated in the positive or negative regulation of these diseases. Clinical and biochemical evidence suggests that secreted PLA2 group III (sPLA2-III) is associated with colorectal cancer, although its precise role remains obscure. Here we have found that sPLA2-III-null (Pla2g3−/−) mice are highly resistant to colon carcinogenesis. Furthermore, Pla2g3−/− mice are less susceptible to dextran sulfate-induced colitis, implying that the amelioration of colonic inflammation by sPLA2-III ablation may underlie the protective effect against colon cancer. Lipidomics analysis of the colon revealed significant reduction of pro-inflammatory/pro-tumorigenic lysophosholipids as well as unusual steady-state elevation of colon-protective fatty acids and their oxygenated metabolites in Pla2g3−/− mice. Overall, our results establish a role of sPLA2-III in the promotion of colorectal inflammation and cancer, expand our understanding of the divergent roles of multiple PLA2 enzymes in the gastrointestinal tract, and point to sPLA2-III as a novel druggable target for colorectal diseases.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
7
Start Page
12261
Published Date
2017-09-25
Remark
Supplemental information : srep_7_12261_s1.pdf
Rights
© The Author(s) 2017
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
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departments
Bioscience and Bioindustry