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

Autor(es)

Simoes Sato, Alex Yuri ^{[1, 2]} ; Antonioli, Eliane ^[1] ; Tambellini, Rodrigo ^[3] ; Campos, Alexandre Holthausen ^[1]

Afiliação do(s) autor(es)

^[1] Inst Israelita Ensino & Pesquisa Albert Einstein, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Physiol & Biophys, BR-05508 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Div Nephrol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY; v. 301, n. 6, p. F1260-F1269, DEC 2011.
• Citações Web of Science: 5

Resumo

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
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto