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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

ID1 inhibits USF2 and blocks TGF-beta-induced apoptosis in mesangial cells

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Simoes Sato, Alex Yuri [1, 2] ; Antonioli, Eliane [2] ; Tambellini, Rodrigo [3] ; Campos, Alexandre Holthausen [2]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Physiol & Biophys, BR-05508 Sao Paulo - Brazil
[2] Inst Israelita Ensino & Pesquisa Albert Einstein, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Div Nephrol, Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Citações Web of Science: 5

Sato AY, Antonioli E, Tambellini R, Campos AH. ID1 inhibits USF2 and blocks TGF-beta-induced apoptosis in mesangial cells. Am J Physiol Renal Physiol 301: F1260-F1269, 2011. First published September 14, 2011; doi: 10.1152/ajprenal.00128.2011.-Mesangial cells (MC) play an essential role in normal function of the glomerulus. Phenotypic changes in MC lead to the development of glomerular diseases such as diabetic nephropathy and glomerulosclerosis. The late phase of diabetic glomerulopathy is characterized by MC death and fibrosis. Current data highlight the transforming growth factor (TGF)-beta as a trigger of the pathological changes observed in MC, including death by apoptosis. However, the mechanisms and mediators involved in this process are still poorly understood. Identification of novel elements involved in MC death may provide a better understanding of the pathophysiology of glomerular diseases. Here, we show that bone morphogenetic proteins (BMPs; known antagonists of the profibrotic effects of TGF-beta in the kidney) strongly induce inhibitor of DNA binding (ID1) mRNA transcription and protein expression in human MC. ID genes have been implicated in cell survival control and are constitutively expressed in MC. We show that BMPs and ID1 exert an anti-apoptotic effect in MC by inhibition of USF2 transcriptional activity. On the other hand, TGF-beta upregulates USF2, increasing BAX (proapoptotic gene) levels and apoptosis rates. Taken together, our results point to a novel molecular pathway that modulates MC apoptosis, which is potentially involved in the pathogenesis of glomerular diseases. (AU)

Processo FAPESP: 06/05818-8 - Identificação e caracterização das interações do gene e proteína ID-1 em células mesangiais humanas
Beneficiário:Alex Yuri Simões Sato
Linha de fomento: Bolsas no Brasil - Doutorado Direto