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Doctoral Thesis
DOI
10.11606/T.42.2013.tde-26092013-093312
Document
Author
Full name
Ana Paula Zen Petisco Fiore
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Gama, Patricia (President)
Armelin, Hugo Aguirre
Carvalho, Hernandes Faustino de
Freitas, Vanessa Morais
Lotfi, Claudimara Ferini Pacicco
Title in Portuguese
Regulação de P27 pelo fator de crescimento transformante b1 (TGFb1) na mucosa gástrica de ratos lactentes.
Keywords in Portuguese
Aleitamento materno
Ciclo celular
Fatores de crescimento
Jejum
Mucosa gástrica
Ratos
Abstract in Portuguese
O leite é essencial para o desenvolvimento pós-natal da mucosa gástrica e durante o período de aleitamento, o jejum estimula a proliferação celular. Mostramos que o TGFb, reverte este efeito e p27 está envolvida neste mecanismo. Os níveis de p27 oscilam durante o ciclo celular, devido à sua fosforilação na Thr187, que leva à degradação pelo sistema UPS. Diferentes estudos relatam que TGFb pode aumentar p27, através do controle de sua degradação. Este estudo visa analisar o efeito do jejum e TGFb1, na regulação de p27 no epitélio gástrico de ratos lactentes. Para tanto, filhotes de 14 dias foram submetidos a jejum durante 90 min e receberam uma dose única de TGFb ou PBS, por gavagem. As amostras foram coletadas após 2 e 14 horas de tratamento. Analisamos a concentração proteica de p27, fosfo-p27, Skp2 e Cdh1. Observamos que durante o jejum houve a diminuição de p27 e Cdh1, paralelamente ao aumento de fosfo-p27 e Skp2. Enquanto que o tratamento com TGFb1, reverteu os efeitos do jejum em 2h e 14h em todas as proteínas analisadas. Além disso, o jejum aumentou a ubiquitinação e degradação de p27 e o tratamento com TGFb1 reverte esses efeitos. Desta forma, o TGFb1 do leite materno estabiliza os níveis de p27 e assim, influenciar a progressão do ciclo celular no epitélio gástrico.
Title in English
Transforming growth factor b1 regulates p27Kip1 post translational levels in the gastric mucosa of suckling rats.
Keywords in English
Breastfeeding
Cell cycle
Fasting
Gastric mucosa
Growth factors
Rats
Abstract in English
Milk is essential for postnatal development of the gastric mucosa and during the suckling period fasting stimulates cell proliferation. We have shown that TGFb reverses this effect and p27 is involved in this mechanism. The levels of p27 oscillate during the cell cycle due to its phosphorylation at Thr187, which leads to its degradation by the UPS. Different studies reported that TGFb can increase p27, by controlling its degradation. This study aims to analyze the effect of fasting and TGFb1 in regulating p27 in lactating rats gastric epithelium. For such, the 14 days rats were fasted for 90 min and received a single dose of TGFb or PBS by gavage. Samples were collected after 2 and 14 hours of treatment. We analyzed the p27 protein concentration, phospho-p27, Skp2 and Cdh1. We found that during fasting, p27 and Cdh1 a decreased, at the same time to the increment of phospho-p27 and Skp2. The treatment with TGFb1, reversed the effects of fasting on 2h and 14h in all proteins analyzed. Moreover, the fasting increased the ubiquitination and the degradation of p27, while TGFb1 treatment reversed these effects. Thus the milk born TGFb1 can stabilize p27 levels and thus influences cell cycle progression in lactent rat gastric epithelium.
 
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Publishing Date
2013-12-06
 
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