The lack of PI3K gamma favors M1 macrophage polarization and does not prevent kidney diseases progression

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art_AMANO_The_lack_of_PI3K_gamma_favors_M1_macrophage_2018.PDF (2.12 MB)
Citações na Scopus
17
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE BV
Autores
AMANO, Mariane T.
CASTOLDI, Angela
ANDRADE-OLIVEIRA, Vinicius
LATANCIA, Marcela T.
TERRA, Fernanda F.
CORREA-COSTA, Matheus
BREDA, Cristiane N. S.
FELIZARDO, Raphael J. F.
PEREIRA, Welbert O.
SILVA, Marina B. da
Citação
INTERNATIONAL IMMUNOPHARMACOLOGY, v.64, p.151-161, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Acute kidney injury (AKI) and chronic kidney disease (CKD) are major concerns in worldwide public health, and their pathophysiology involves immune cells activation, being macrophages one of the main players of both processes. It is suggested that metabolic pathways could contribute to macrophage modulation and phosphatidylinositol-3 kinase (PI3K) pathway was shown to be activated in kidneys subjected to ischemia and reperfusion as well as unilateral ureteral obstruction (UUO). Although PI3K inhibition is mostly associated with anti-inflammatory response, its use in kidney injuries has been shown controversial results, which indicates the need for further studies. Our aim was to unveil the role of PI3K gamma in macrophage polarization and in kidney diseases development. We analyzed bone-marrow macrophages polarization from wild-type (WT) and PI3K gamma knockout (PI3K KO) animals. We observed increased expression of M1 (CD86, CCR7, iNOS, TNF, CXCL9, CXCL10, IL-12 and IL-23) and decreased of M2 (CD206, Arg-1, FIZZ1 and YM1) markers in the lack of PI3K gamma. And this modulation was accompanied by higher levels of inflammatory cytokines in PI3K KO M1 cells. PI3K KO mice had increased M1 in steady state kidneys, and no protection was observed in these mice after acute and chronic kidney insults. On the contrary, they presented higher levels of protein-to-creatinine ratio and Kim-1 expression and increased tubular injury. In conclusion, our findings demonstrated that the lack of PI3K gamma favors M1 macrophages polarization providing an inflammatory-prone environment, which does not prevent kidney diseases progression.
Palavras-chave
PI3K, Macrophage, Acute kidney injury, Chronic kidney disease
URI
https://observatorio.fm.usp.br/handle/OPI/30292
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Coleções
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - ODS/03