title: TBX3, a downstream target of TGF-β1, inhibits mesangial cell apoptosis.
abstract: Chronic kidney disease (CKD) is an increasingly common condition characterized by progressive loss of functional nephrons leading to renal failure. TGF-β1-induced mesangial cell (MC) phenotype alterations have been linked to the genesis of CKD. Here we show that TGF-β1 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-β1, 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-β1 induces glomerulosclerosis and tubular fibrosis during the progression of nephropathies.
authors.affiliation: Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, 2SS/Bloco A., São Paulo, São Paulo CEP 05651-901, Brazil; Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Lislaine A
authors.initials: LA
authors.lastname: Wensing
authors.affiliation: Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, 2SS/Bloco A., São Paulo, São Paulo CEP 05651-901, Brazil. Electronic address: alexandre.campos@einstein.br.
authors.forename: Alexandre H
authors.initials: AH
authors.lastname: Campos
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D050527:Mesangial Cells / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D024141:Collagen Type IV; D005353:Fibronectins; D020033:Protein Isoforms; D020825:T-Box Domain Proteins; C106884:TBX3 protein, human; D053773:Transforming Growth Factor beta1
keywords: Apoptosis; Mesangial cells; TBX3; TGF-β1