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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2015

Contributo in rivista

Tipo: Articolo in rivista

Titolo: A gut microbial metabolite of linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, ameliorates intestinal epithelial barrier impairment partially via GPR40-MEK-ERK pathway

Anno di pubblicazione: 2015

Formato: Cartaceo

Autori: Miyamoto, Junki; Mizukure, Taichi; Park, Sibum; Kishino, Shigenobu; Kimura, Ikuo; Hirano, Kanako; Bergamo, Paolo; Rossi, Mauro; Suzuki, Takuya; Arita, Makoto; Ogawa, Jun; Tanabe, Soichi

Affiliazioni autori: Hiroshima University; Kyoto University; Tokyo University of Agriculture and Technology; Consiglio Nazionale delle Ricerche; Riken

Autori CNR:


Lingua: inglese

Abstract: Gut microbial metabolites of polyunsaturated fatty acids (PUFAs) 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 (IBD). We evaluated the effects of five novel gut microbial metabolites on tumor necrosis factor (TNF)-?-induced barrier impairment in Caco-2 cells and dextran sulfate sodium (DSS)-induced colitis in mice. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a gut microbial metabolite of linoleic acid, suppressed TNF-? and DSS-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 (TNFR) 2 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 [Ca2+]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. On the other hand, 10-hydroxyoctadacanoic acid (HYB), which is a gut microbial metabolite of oleic acid and lacks a carbon-carbon double bond at ?12 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 IBD.

Lingua abstract: inglese

Pagine da: 2902

Pagine a: 2918


The Journal of biological chemistry American Society for Biochemistry and Molecular Biology [etc.]
Paese di pubblicazione: Stati Uniti d'America
Lingua: inglese
ISSN: 0021-9258

Numero volume: 290

Numero fascicolo: 5

DOI: 10.1074/jbc.M114.610733

Referee: Sì: Internazionale

Stato della pubblicazione: Published version

Indicizzato da: Scopus [2-s2.0-84921841372]

Parole chiave:

  • Caco-2
  • colitis
  • epithelial cell
  • G protein-coupled receptor
  • microbiome
  • linoleic acid
  • metabolite
  • tight junction
  • tumor necrosis factor (TNF)

URL: http://www.scopus.com/record/display.url?eid=2-s2.0-84921841372&origin=inward

Strutture CNR:


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