A gut microbial metabolite of linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, ameliorates intestinal epithelial barrier impairment partially via GPR40-MEK-ERK pathway
Miyamoto J, Mizukure T, Park SB, Kishino S, Kimura I, Hirano K, Bergamo P, Rossi M, Suzuki T, Arita M, Ogawa J, Tanabe S
The Journal of biological chemistry · 200 citas
Etiquetas de revisión
Solo mecanismosDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Solo mecanismos
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- Japan Society for the Promotion of Science
- Gobierno
- Bio-oriented Technology Research Advancement Institution
- Subvenciones
- Japan Society for the Promotion of Science (22380076); Japan Society for the Promotion of Science (25292074); Japan Society for the Promotion of Science (14J06559)
Según 2 financiadores declarados.
Publicación
- Publicado
- 2014-12-11 · J Biol Chem · vol. 290 · número 5 · págs. 2902–2918
- Editorial
- Elsevier BV
- Citado
- 269 citas · más que el 97% de estudios similares · 5.4× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 64 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Gut microbiota and health · Helicobacter pylori-related gastroenterology studies · Barrier Structure and Function Studies
- Palabras clave
- Linoleic acid, Chemistry, Biochemistry, MAPK/ERK pathway, Metabolite, Tumor necrosis factor alpha, Conjugated linoleic acid, Biology, Signal transduction, Fatty acid, Endocrinology
- MeSH
- intestines, caco-2 cells, epithelial cells, animals, mice, inbred balb c, humans, mice, colitis, linoleic acid, oleic acids, receptors, g-protein-coupled, flow cytometry, immunohistochemistry, map kinase signaling system, female
12 autores
- Junki Miyamoto🇯🇵Hiroshima University
- Taichi Mizukure🇯🇵Hiroshima University
- Si-Bum Park🇯🇵Kyoto University
- Shigenobu Kishino🇯🇵Kyoto University
- Ikuo Kimura🇯🇵Kyoto University; Tokyo University of Agriculture and Technology
- Kanako Hirano🇯🇵Kyoto University
- Paolo Bergamo🇮🇹Institute of Food Science; National Research Council
- Mauro Rossi🇮🇹Institute of Food Science; National Research Council
- Takuya Suzuki🇯🇵Hiroshima University
- Makoto Arita🇯🇵RIKEN Center for Integrative Medical Sciences
- Jun Ogawa🇯🇵 · autor de correspondenciaKyoto University
- Soichi Tanabe🇯🇵 · autor de correspondenciaHiroshima University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Gut microbial metabolites of polyunsaturated fatty acids have attracted much attention because of their various physiological properties. Dysfunction of tight junction (TJ) in the intestine contributes to the pathogenesis of many disorders such as inflammatory bowel disease. We evaluated the effects of five novel gut microbial metabolites on tumor necrosis factor (TNF)-α-induced barrier impairment in Caco-2 cells and dextran sulfate sodium-induced colitis in mice. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a gut microbial metabolite of linoleic acid, suppressed TNF-α and dextran sulfate sodium-induced changes in the expression of TJ-related molecules, occludin, zonula occludens-1, and myosin light chain kinase. HYA also suppressed the expression of TNF receptor 2 (TNFR2) mRNA and protein expression in Caco-2 cells and colonic tissue. In addition, HYA suppressed the protein expression of TNFR2 in murine intestinal epithelial cells. Furthermore, HYA significantly up-regulated G protein-coupled receptor (GPR) 40 expression in Caco-2 cells. It also induced [Ca(2+)]i responses in HEK293 cells expressing human GPR40 with higher sensitivity than linoleic acid, its metabolic precursor. The barrier-recovering effects of HYA were abrogated by a GPR40 antagonist and MEK inhibitor in Caco-2 cells. Conversely, 10-hydroxyoctadacanoic acid, which is a gut microbial metabolite of oleic acid and lacks a carbon-carbon double bond at Δ12 position, did not show these TJ-restoring activities and down-regulated GPR40 expression. Therefore, HYA modulates TNFR2 expression, at least partially, via the GPR40-MEK-ERK pathway and may be useful in the treatment of TJ-related disorders such as inflammatory bowel disease.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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