GSK-3ß inhibitor attenuates urinary albumin excretion in type 2 diabetic db/db mice, and delays epithelial-to-mesenchymal transition in mouse kidneys and podocytes.
Mol Med Rep
; 14(2): 1771-84, 2016 Aug.
Article
em En
| MEDLINE
| ID: mdl-27357417
ABSTRACT
The mechanism underlying epithelialtomesenchymal transition (EMT) caused by high glucose (HG) stimulation in diabetic nephropathy (DN) remains to be fully elucidated. The present study investigated the effects of HG on EMT and the activity of glycogen synthase kinase 3ß (GSK3ß) in podocytes and the kidneys of db/db mice, and assessed the effects of (2'Z, 3'E)6bromoindirubin3'oxime (BIO), an inhibitor of GSK3ß, on EMT and glomerular injury. The resulting data showed that the activity of GSK3ß was upregulated by HG and downregulated by BIO in the podocytes and the renal cortex. The expression levels of epithelial markers, including nephrin, podocin and synaptopodin, were decreased by HG and increased by BIO, whereas the reverse were true for mesenchymal markers, including αsmooth muscle actin (αSMA) and fibronectin. The expression levels of ßcatenin and Snail, in contrast to current understanding of the Wnt signaling pathway, were increased by HG and decreased by BIO. In addition, expression of the vitamin D receptor (VDR) was decreased by HG and increased by BIO. In conclusion, the present study revealed that the mechanism by which BIO inhibited HGmediated EMT in podocytes and the renal cortex was primarily due to the VDR. Treatment with BIO protected renal function by maintaining the integrity of the filtration membrane and decreasing UAE, but not by regulating blood glucose. Therefore, GSK3ß may be used as a sensitive biomarker of DN, and its inhibition by BIO may be effective in the treatment of DN.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteinúria
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Diabetes Mellitus Tipo 2
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Nefropatias Diabéticas
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Podócitos
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Transição Epitelial-Mesenquimal
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Glicogênio Sintase Quinase 3 beta
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2016
Tipo de documento:
Article