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| Author(s): |
Lislaine Andrade Wensing
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2013-03-07 |
| Examining board members: |
Alexandre Holthausen Campos;
Guiomar Nascimento Gomes;
Antonio Jose Barros Magaldi;
Júlio Cesar Martins Monte;
Rildo Aparecido Volpini
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| Advisor: | Alexandre Holthausen Campos |
| Abstract | |
Mesangial cells (MC) are essential for glomerular homeostasis. In addition, MC play a significant role in the development of glomerulosclerosis of chronic nephropathies. We demonstrated that the transcription repressor TBX3 isoforms, TBX3.1 and TBX3 + 2<font face=\"Symbol\">a, were upregulated by low concentrations of TGF-<font face=\"Symbol\">b1. Selective overexpression of the isoforms did not affect MC proliferation or extracellular matrix production. However, TBX3 forced expression decreased apoptosis induced by FBS deprivation. Moreover, TBX3 gene silencing sensitized MC to the proapoptotic stimulus caused by SBF withdrawal. Finally, we observed an increase in TBX3 protein expression in glomerular and tubular regions in a model of chronic nephropathy (5/6 nephrectomy), temporally related to increased expression of TGF-<font face=\"Symbol\">b1, collagen IV and fibronectin. Our results indicate that TBX3 acts as an antiapoptotic factor in MC in vitro and may be involved in the mechanism by which TGF-<font face=\"Symbol\">b1 induces glomerulosclerosis and tubular fibrosis during the progression of nephropathies. (AU) | |