TBX3, a downstream target of TGF-ß1, inhibits mesangial cell apoptosis.
Exp Cell Res
; 328(2): 340-50, 2014 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-25158279
Chronic kidney disease (CKD) is an increasingly common condition characterized by progressive loss of functional nephrons leading to renal failure. TGF-ß1-induced mesangial cell (MC) phenotype alterations have been linked to the genesis of CKD. Here we show that TGF-ß1 regulates TBX3 gene expression in MC. This gene encodes for two main isoforms, TBX3.1 and TBX3+2α. TBX3.1 has been implicated in cell immortalization, proliferation and apoptosis by inhibiting p14(ARF)-Mdm2-p53 pathway, while TBX3+2α role has not been defined. We demonstrated that TBX3 overexpression abrogated MC apoptosis induced by serum deprivation. Moreover, we observed an enhancement in TBX3 protein expression both in glomerular and tubular regions in the model of 5/6 nephrectomy, temporally related to increased expression of TGF-ß1, type IV collagen and fibronectin. Our results indicate that TBX3 acts as an anti-apoptotic factor in MC in vitro and may be involved in the mechanism by which TGF-ß1 induces glomerulosclerosis and tubular fibrosis during the progression of nephropathies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Proteínas com Domínio T
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Células Mesangiais
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Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos