miR-218 regulates diabetic nephropathy via targeting IKK-ß and modulating NK-κB-mediated inflammation.
J Cell Physiol
; 235(4): 3362-3371, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31549412
ABSTRACT
Diabetic nephropathy (DN) is a common clinically relevant complication of diabetes that is associated with damage to the capillaries, yet the etiology of this condition remains unclear. Nuclear factor-kappa B (NF-κB) activation is known to be associated with DN-related inflammation and disease progression. Recent work indicated that microRNAs are diagnostic biomarkers of DN progression associated with inï¬ammation in the progression of DN. miR-218 is known to play key regulatory roles in certain cancers in humans, while its influence on DN pathology remains uncertain. The present study, therefore, sought to assess how miR-218 influences the progression of disease in both a rat streptozotocin-induced model of DN and as well as an in vitro model system in which mouse podocytes were stimulated with high glucose levels. We found miR-218 to be markedly downregulated in both model systems relative to appropriate controls, and this downregulation was associated with IKK-ß upregulation. In DN rat model, overexpressing miR-218 was sufficient to reduce renal injury. We further determined that podocyte proliferation was markedly impaired by glucose treatment, leading to the apoptotic death of these cells, and miR-218 mimics were able to reduce these phenotypes. Overexpressing miR-218 also significantly dampened inflammatory responses in this model system, as evidenced by reduced tumor necrosis factor-α, interleukin-6 (IL-6), IL-1ß, and MCP-1 levels. We then confirmed that miR-218 targeting the messenger RNA encoding IKK-ß using a dual-luciferase reporter assay. Together, our results provide clear evidence that miR-218 regulate NF-κB-mediated inflammation, which is central to DN progression.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Diabetes Mellitus Experimental
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Nefropatias Diabéticas
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Quinase I-kappa B
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Inflamação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China