Dact1, a Wnt-Pathway Inhibitor, Mediates Human Mesangial Cell TGF-ß1-Induced Apoptosis.
J Cell Physiol
; 232(8): 2104-2111, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-27714812
Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of men and women of all ages and racial groups. Loss of mesangial cells (MC) represents an early common feature in the pathogenesis of CKD. Transforming growth factor-ß1 (TGF-ß1) is a key inducer of kidney damage and triggers several pathological changes in renal cells, notably MC apoptosis. However, the mechanism of MC apoptosis induced by TGF-ß1 remains elusive. Here, we demonstrate for the first time a novel regulatory pathway in which the disheveled-binding antagonist of ß-catenin 1 (Dact1) gene is upregulated by TGF-ß1, inducing MC apoptosis. We also show that the inhibitory effect of Dact1 and TGF-ß1 on the transcriptional activation of the pro-survival Wnt pathway is the mechanism of death induction. In addition, Dact1 mRNA/protein levels are increased in kidney remnants from 5/6 nephrectomized rats and strongly correlate with TGF-ß1 expression. Together, our results point to Dact1 as a novel element controlling MC survival that is causally related to CKD progression. J. Cell. Physiol. 232: 2104-2111, 2017. © 2016 Wiley Periodicals, Inc.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Apoptose
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Proteínas Adaptadoras de Transdução de Sinal
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Células Mesangiais
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Insuficiência Renal Crônica
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Fator de Crescimento Transformador beta1
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Via de Sinalização Wnt
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article