Assuntos
Angiodisplasia , Hemorragia Gastrointestinal , Mieloma Múltiplo , Doença de von Willebrand Tipo 2 , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Angiodisplasia/complicações , Hemorragia Gastrointestinal/etiologia , Doença de von Willebrand Tipo 2/complicações , Doença de von Willebrand Tipo 2/tratamento farmacológico , Intestino Delgado/patologia , Masculino , Feminino , Dexametasona/uso terapêutico , Idoso , Pessoa de Meia-Idade , Talidomida/uso terapêuticoRESUMO
AIM: Chronic kidney disease (CKD) is associated with an inflammation-mediated process, and the vitamin D (3) catabolizing enzyme, CYP24, is frequently overexpressed in CKD, where it may play a crucial role in kidney disease. METHODS: Herein, in this study, we investigated CYP24, reactive oxygen species (ROS), and inflammatory responses in an indoxyl sulfate (IS)-induced CKD model to elucidate the role of CYP24 in CKD. RESULTS: Our results showed that IS upregulates proinflammatory cytokine, CYP24 and nuclear factor-κB (NF-κB) expression in human renal proximal tubule epithelial cells. In addition, IS treatment increased ROS production and simultaneously upregulated CYP24 expression and NF-κB translocation. Moreover, the IS-induced upregulation of CYP24 expression was alleviated by an inhibitor of NF-κB, as well as a siRNA specific to NF-κB p65. Furthermore, the renal cortex of DN (Dahl salt-resistant normotensive) + IS, DH (Dahl salt-sensitive hypertensive), and DH + IS rats showed increased expression of NF-κB p65, CYP24, 8-hydroxydeoxyguanosine (8-OHdG), a marker of ROS and macrophage infiltration compared with DN rats. CONCLUSIONS: These results provide evidence that administration of IS in human renal tubular epithelial cells upregulates NF-κB, which leads to increase CYP24 expression and ROS production. They also suggest that suppressing NF-κB signalling is promising for the development into a strategy for CKD treatment.