Blocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosis

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dc.creatorFranciel Batistafelix
dc.creatorFlávio Almeida Amaral
dc.creatorFrederico Marianetti Soriani
dc.creatorMauro Martins Teixeira
dc.creatorVanessa Pinho
dc.creatorJulia Dias
dc.creatorJuliana Priscila Vago
dc.creatorDébora Gonzaga Martins
dc.creatorVinícius Amorim Beltrami
dc.creatorDébora de Oliveira Fernandes
dc.creatorAnna Clara Paiva Menezes Dos Santos
dc.creatorCelso Martins Queiroz-junior
dc.creatorLirlândia Pires de Sousa
dc.date.accessioned2025-01-21T20:38:07Z
dc.date.accessioned2025-09-08T23:14:57Z
dc.date.available2025-01-21T20:38:07Z
dc.date.issued2023-02
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1016/j.phrs.2022.106640
dc.identifier.issn1096-1186
dc.identifier.urihttps://hdl.handle.net/1843/79379
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofPharmacological Research
dc.rightsAcesso Aberto
dc.subjectApoptose
dc.subjectInflamação
dc.subjectGenética
dc.subject.otherEfferocytosis
dc.subject.otherApoptosis
dc.subject.otherInflammation
dc.subject.otherArthritis
dc.subject.otherInflammation resolution
dc.titleBlocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosis
dc.typeArtigo de periódico
local.citation.epage16
local.citation.spage1
local.citation.volume188
local.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.
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS
local.publisher.departmentICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA
local.publisher.departmentICB - DEPARTAMENTO DE FARMACOLOGIA
local.publisher.departmentICB - DEPARTAMENTO DE MORFOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S1043661822005862?via%3Dihub

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