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

• Published in: Experimental cell research Vol. 328; no. 2; p. 340
• Main Authors: Wensing, Lislaine A, Campos, Alexandre H
• Format: Journal Article
• Language: English
• Published: New York Elsevier BV 01.11.2014
• Subjects: Apoptosis; Gene expression; Kidney diseases; Proteins; Signal transduction
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2014.08.022

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+2α. TBX3.1 has been implicated in cell immortalization, proliferation and apoptosis by inhibiting p14ARF -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-[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. * TBX3 isoforms are upregulated by TGF-b1 in mesangial cells. * TBX3 isoforms have different subcellular distribution profile in mesangial cells. * TBX3 isoforms exhibit antiapoptotic action in mesangial cells. * TBX3 protein is overexpressed in a model of nephropathy (5/6 nephrectomy).