title: Ghrelin attenuates intestinal ischemia/reperfusion injury in mice by activating the mTOR signaling pathway.
abstract: Intestinal ischemia/reperfusion (I/R) injury is a serious condition in intensive care patients, resulting in severe inflammation and remote organ damage. The activation of the mammalian target of rapamycin (mTOR)/p70 ribosomal S6 kinase (p70S6K) signaling pathway exerts protective effect against ischemia/reperfusion injury. Ghrelin, an orexigenic hormone, inhibits the release of pro-inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor-α and IL-6. In this study, we investigated the effects of ghrelin on gut I/R injury and the regulation of the mTOR/p70S6K signaling pathway following gut I/R injury in mice. C57BL/6 mice underwent superior mesenteric artery occlusion for 45 min, followed by reperfusion for 4 h. Ghrelin was administered at the onset of reperfusion. We assessed survival, organ injury variables, pro-inflammatory cytokine expression and observed the histological changes of the small intestine and lungs. Our results revealed that the administration of ghrelin inhibited the release of certain pro-inflammatory cytokines, reduced neutrophil infiltration, attenuated organ injury and improved survival following gut I/R injury. The administration of D-Lys-GHRP6, a specific ghrelin receptor antagonist, to a certain extent, counteracted the protective effects of ghrelin in gut I/R-induced organ injury and mortality. To determine whether the beneficial effects of ghrelin following gut I/R injury are associated with the mTOR/p70S6K signaling pathway, the phosphorylation levels of mTOR and p70S6K were detected by western blot analysis. Our results revealed that mTOR and p70S6K phosphorylation increased in the tissue from the small intestine and pulmonary tissue in the animals treated with ghrelin. These findings suggest that ghrelin attenuates organ injury following gut I/R by promoting the activation of the mTOR/p70S6K signaling pathway.
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Cui
authors.forename: Guangwei
authors.initials: G
authors.lastname: Luo
authors.forename: Jiaheng
authors.initials: J
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Na
authors.initials: N
authors.lastname: Hu
authors.forename: Tianpen
authors.initials: T
authors.lastname: Cui
mesh_terms: D000818:Animals; D054439:Ghrelin / Q000097:blood / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D054439:Ghrelin; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; C546843:mTOR protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases