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Doctoral Thesis
DOI
10.11606/T.42.2011.tde-22072011-124216
Document
Author
Full name
Alex Yuri Simões Sato
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Campos, Alexandre Holthausen (President)
Reboucas, Nancy Amaral
Santos, Oscar Fernando Pavao dos
Schor, Nestor
Silva, Silvana Auxiliadora Bordin da
Title in Portuguese
Identificação e caracterização das interações do gene ID1 em células mesangiais humanas.
Keywords in Portuguese
Biologia molecular
Células cultivadas
Fisiologia renal
Nefropatias
Regulação gênica
Sobrevivência celular
Abstract in Portuguese
As células mesangiais (CM) apresentam papel essencial na fisiologia glomerular normal, e alterações em seu fenótipo levam ao desenvolvimento de glomerulopatias. A fase tardia da glomerulopatia diabética é caracterizada por fibrose e morte por apoptose das CM. Portanto, a identificação de novos elementos envolvidos nas modificações patológicas das CM facilitaria a compreensão da fisiopatologia das doenças glomerulares. A família de genes ID está implicada em processos celulares distintos, como proliferação, diferenciação e apoptose. O presente estudo tem por finalidade investigar as interações do gene ID1, com o DNA e/ou proteínas, em CM humanas. Aqui demonstramos que Id1 interage com o fator de transcrição USF2, inibindo sua atividade transcricional. Adicionalmente, demonstramos que BMP-7 e Id1 antagonizam a morte celular induzida por TGFb-1 por inibir a atividade de USF2. Nossos dados apontam para uma nova via molecular portencialmente relevante para o melhor entendimento da patogênese das doenças renais crônicas.
Title in English
Identification and characterization of ID1 gene interactions in human mesangial cells.
Keywords in English
Cell survival
Cultured cells
Gene regulation
Molecular biology
Nephropathy
Renal physiology
Abstract in English
Mesangial cells (MC) play an essential role in normal function of the glomerulus. Phenotypic changes in MC lead to the development of glomerophaties. The late phase of diabetic glomerulopathy is characterized by fibrosis and death of MC. Thus, the identification of novel elements involved in these alterations would facilitate the comprehension of the pathophysiology of glomerular diseases. The ID (Inhibitors of DNA binding) family of genes has been implicated in diverse cellular processes, such as proliferation, differentiation, and apoptosis control. This study aims to investigate the interactions of ID1, with DNA or proteins, in human mesangial cells. We demonstrated that Id1 binds specifically to the transcription factor USF2. In addition, we show that BMP-7 and Id1 antagonize TGFb-1 induced death by inhibiting USF2 activity in human MC. In conclusion, our results point to a novel molecular path involved in the pathogenesis of glomerular diseases.
 
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Publishing Date
2011-08-24
 
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