Loss of endothelial glucocorticoid receptor accelerates diabetic nephropathy.
Nat Commun
; 12(1): 2368, 2021 04 22.
Article
em En
| MEDLINE
| ID: mdl-33888696
ABSTRACT
Endothelial cells play a key role in the regulation of disease. Defective regulation of endothelial cell homeostasis may cause mesenchymal activation of other endothelial cells or neighboring cell types, and in both cases contributes to organ fibrosis. Regulatory control of endothelial cell homeostasis is not well studied. Diabetes accelerates renal fibrosis in mice lacking the endothelial glucocorticoid receptor (GR), compared to control mice. Hypercholesterolemia further enhances severe renal fibrosis. The fibrogenic phenotype in the kidneys of diabetic mice lacking endothelial GR is associated with aberrant cytokine and chemokine reprogramming, augmented Wnt signaling and suppression of fatty acid oxidation. Both neutralization of IL-6 and Wnt inhibition improve kidney fibrosis by mitigating mesenchymal transition. Conditioned media from endothelial cells from diabetic mice lacking endothelial GR stimulate Wnt signaling-dependent epithelial-to-mesenchymal transition in tubular epithelial cells from diabetic controls. These data demonstrate that endothelial GR is an essential antifibrotic molecule in diabetes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Glucocorticoides
/
Nefropatias Diabéticas
/
Endotélio
/
Hipercolesterolemia
/
Túbulos Renais
Tipo de estudo:
Etiology_studies
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2021
Tipo de documento:
Article