TBX3, a downstream target of TGF-beta 1, inhibits mesangial cell apoptosis

Autor(es)

Wensing, Lislaine A. ^{[1, 2]} ; Campos, Alexandre H. ^[1]

Afiliação do(s) autor(es)

^[1] Hosp Israelita Albert Einstein, BR-05651901 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Cell Research; v. 328, n. 2, p. 340-350, NOV 1 2014.
• Citações Web of Science: 4

Resumo

Chronic kidney disease (CKD) is an increasingly common condition characterized by progressive loss of functional nephrons leading to renal failure. TGF-beta 1-induced mesangial cell (MC) phenotype alterations have been linked to the genesis of CKD. Here we show that TGF-beta 1 regulates TBX3 gene expression in MC. This gene encodes for two main isoforms, TBX3.1 and TBX3+2 alpha. TBX3.1 has been implicated in cell immortalization, proliferation and apoptosis by inhibiting p14(ARF)-Mdm2-p53 pathway, while TBX3+2 alpha 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-beta 1, 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-beta 1 induces glomerulosclerosis and tubular fibrosis during the progression of nephropathies. (C) 2014 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 07/02864-1 - Regulação do gene TBX3 por TGF-b1 em células mesangiais
• Beneficiário: Lislaine Andrade Wensing
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto