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Cells ; 11(4)2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35203394

RESUMO

Obesity causes renal changes (ORC), characterized by defective renal autophagy, lipogenesis, enhanced macrophage infiltration and apoptosis. We hypothesize that Dasatinib, a tyrosine kinase inhibitor, may ameliorate changes associated with obesity. We the mice with either Obesogenic diet (OD) or a standard basal diet. After 12 weeks, the mice received either vehicle or Dasatinib 4 mg/kg/d for an additional four weeks. We examined serum creatinine, urea, lipid profile and renal cortical mRNA expression for lipogenesis marker SREBP1, inflammatory macrophage marker iNOS and fibrosis markers; TGFß and PDGFA genes; immunohistochemical (IHC) staining for CD68; inflammatory macrophage marker and ASMA; fibrosis marker, LC3 and SQSTM1/P62; autophagy markers and western blotting (WB) for caspase-3; and, as an apoptosis marker, LC3II/I and SQSTM1/P62 in addition to staining for H&E, PAS, Sirius red and histopathological scoring. Dasatinib attenuated renal cortical mRNA expression for SREBP1, iNOS, PDGFA and TGFß and IHC staining for CD68, ASMA and SQSTM1/P62 and WB for caspase-3 and SQSTM1/P62, while elevating LC3 expression. Moreover, Dasatinib ameliorated ORC; glomerulosclerosis, glomerular expansion, tubular dilatation, vacuolation and casts; inflammatory cellular infiltration; and fibrosis. Dasatinib is a promising therapy for ORC by correcting autophagy impairment, attenuating lipogenesis, apoptosis and macrophage infiltration by inducing antifibrotic activity.


Assuntos
Apoptose , Autofagia , Animais , Caspase 3/metabolismo , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Fibrose , Rim/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico , RNA Mensageiro , Proteína Sequestossoma-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo
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