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Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/79379
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dc.creatorFranciel Batistafelixpt_BR
dc.creatorFlávio Almeida Amaralpt_BR
dc.creatorFrederico Marianetti Sorianipt_BR
dc.creatorMauro Martins Teixeirapt_BR
dc.creatorVanessa Pinhopt_BR
dc.creatorJulia Diaspt_BR
dc.creatorJuliana Priscila Vagopt_BR
dc.creatorDébora Gonzaga Martinspt_BR
dc.creatorVinícius Amorim Beltramipt_BR
dc.creatorDébora de Oliveira Fernandespt_BR
dc.creatorAnna Clara Paiva Menezes Dos Santospt_BR
dc.creatorCelso Martins Queiroz-juniorpt_BR
dc.creatorLirlândia Pires de Sousapt_BR
dc.date.accessioned2025-01-21T20:38:07Z-
dc.date.available2025-01-21T20:38:07Z-
dc.date.issued2023-02-
dc.citation.volume188pt_BR
dc.citation.spage1pt_BR
dc.citation.epage16pt_BR
dc.identifier.doihttps://doi.org/10.1016/j.phrs.2022.106640pt_BR
dc.identifier.issn1096-1186pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/79379-
dc.description.resumoInflammation resolution is an active process that involves cellular events such as apoptosis and efferocytosis, which are key steps in the restoration of tissue homeostasis. Hepatocyte growth factor (HGF) is a growth factor mostly produced by mesenchymal-origin cells and has been described to act via MET receptor tyrosine kinase. The HGF/MET axis is essential for determining the progression and severity of inflammatory and immunemediated disorders. Here, we investigated the effect of blocking the HGF/MET signalling pathway by PF04217903 on the resolution of established models of neutrophilic inflammation. In a self-resolving model of gout induced by MSU crystals, HGF expression on periarticular tissue peaked at 12 h, the same time point that neutrophils reach their maximal accumulation in the joints. The HGF/MET axis was activated in this model, as demonstrated by increased levels of MET phosphorylation in neutrophils (Ly6G+ cells). In addition, the number of neutrophils was reduced in the knee exudate after PF-04217903 treatment, an effect accompanied by increased neutrophil apoptosis and efferocytosis and enhanced expression of Annexin A1, a key molecule for inflammation resolution. Reduced MPO activity, IL-1β and CXCL1 levels were also observed in periarticular tissue. Importantly, PF-04217903 reduced the histopathological score and hypernociceptive response. Similar findings were obtained in LPS-induced neutrophilic pleurisy. In human neutrophils, the combined use of LPS and HGF increased MET phosphorylation and provided a prosurvival signal, whereas blocking MET with PF04217903 induced caspase-dependent neutrophil apoptosis. Taken together, these data demonstrate that blocking HGF/MET signalling may be a potential therapeutic strategy for inducing the resolution of neutrophilic inflammatory responses.pt_BR
dc.format.mimetypepdfpt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICASpt_BR
dc.publisher.departmentICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIApt_BR
dc.publisher.departmentICB - DEPARTAMENTO DE FARMACOLOGIApt_BR
dc.publisher.departmentICB - DEPARTAMENTO DE MORFOLOGIApt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofPharmacological Researchpt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectEfferocytosispt_BR
dc.subjectApoptosispt_BR
dc.subjectInflammationpt_BR
dc.subjectArthritispt_BR
dc.subjectInflammation resolutionpt_BR
dc.subject.otherApoptosept_BR
dc.subject.otherInflamaçãopt_BR
dc.subject.otherGenéticapt_BR
dc.titleBlocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosispt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://www.sciencedirect.com/science/article/pii/S1043661822005862?via%3Dihubpt_BR
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