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

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

Author Simoes Sato, Alex Yuri Google Scholar
Antonioli, Eliane Google Scholar
Tambellini, Rodrigo Autor UNIFESP Google Scholar
Campos, Alexandre Holthausen Google Scholar
Institution Universidade de São Paulo (USP)
Inst Israelita Ensino & Pesquisa Albert Einstein
Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords diabetes
diabetic nephropathy
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
SBIB Albert Einstein
Grant number FAPESP: 06/05818-8
Date 2011-12-01
Published in American Journal of Physiology-renal Physiology. Bethesda: Amer Physiological Soc, v. 301, n. 6, p. F1260-F1269, 2011.
ISSN 1931-857X (Sherpa/Romeo, impact factor)
Publisher Amer Physiological Soc
Extent F1260-F1269
Origin http://dx.doi.org/10.1152/ajprenal.00128.2011
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000298152200013
URI http://repositorio.unifesp.br/handle/11600/34257

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