Regulação do gene TBX3 por TGF-b1 em células mesangiais.

摘要: WENSING, L. A. Regulation of TBX3 gene by TGF-β1 in mesangial cells. 2012. 91 p. Ph. D. thesis (Human Physiology) Instituto de Ciencias Biomedicas, Universidade Sao Paulo, 2013. Mesangial cells (MC) synthesize extracellular matrix (ECM), providing structural support to the glomerular capillaries, and participate regulation filtration rate. During progression nephropathies, MC assume a myofibroblastic phenotype, characterized changes proliferation, apoptosis ECM production, which reflect modifications their expression pattern. Using DNA microarrays, we identified as upregulated stimulated with fetal bovine serum (FBS), condition display phenotype similar that observed nephropathies. is transcriptional repressor containing binding domain (T-box), binds consensus T-site present promoter region target genes. This encodes for two isoforms, TBX3.1 + 2α, generated alternative splicing, exon 2α inserted into middle sequence corresponding its T-box domain. In CM, was low concentrations preferentially through post-transcriptional mechanism. when overexpressed separately adenoviral transduction, showed distinct subcellular localizations: localized nucleus detected cytoplasm. Overexpression isoforms did not affect proliferation or production MC. However, both forms decreased induced FBS deprivation. TBX3.1, particular, reduced level cell death next maintained medium supplemented FBS. Moreover, silencing sensitized proapoptotic stimuli caused removal, increase, although modestly, rates even under pro-survival presence Finally, an increase protein tubular regions model diabetic nephropathy (5/6 nephrectomy), temporally related increased TGF-β1, collagen IV fibronectin. Our results indicate acts antiapoptotic factor vitro may be involved mechanism induces glomerulosclerosis fibrosis during