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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2009.tde-06102009-104706
Document
Author
Full name
Luciana Harumi Osaki
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Gama, Patricia (President)
Bevilacqua, Estela Maris Andrade Forell
Carbonare, Solange Barros
Castelucci, Patricia
Nunes, Fabio Daumas
Title in Portuguese
O papel do alimento, do fator de crescimento transformante alfa e do receptor do fator de crescimento epidermal na proliferação e diferenciação celular durante o desenvolvimento pós-natal do epitélio gástrico de ratos.
Keywords in Portuguese
Diferenciação celular
Estômago de animal
Fatores de crescimento transformantes alfa
Histologia
Proliferação celular
Ratos
Receptores do fator de crescimento epidermal
Abstract in Portuguese
O desmame precoce (DP) causa mudanças na mucosa gástrica, como o aumento da proliferação celular e da expressão do Fator de Crescimento Transformante (TGFa). Neste trabalho, avaliamos o papel desse peptídeo e seu receptor EGFR no controle do crescimento gástrico. Ratos com 15 dias de vida foram divididos em: amamentados (controle) e DP, no qual os filhotes foram separados da mãe e alimentados com pasta de ração. O DP aumentou o número de células marcadas para EGFR, acelerou a diferenciação de células mucosas do colo e elevou a expressão de mucina 6. A inibição do EGFR com AG1478 diminuiu a proliferação celular e o número de células mucosas do colo. Entre as proteínas envolvidas na sinalização de EGFR e ciclo celular, detectamos que o DP elevou os níveis de p-ERK1/2 e p-Src e não alterou p-Akt, p21 e p27. Nós sugerimos que o padrão alimentar influencia a proliferação e diferenciação no epitélio gástrico, e que TGFa/EGFR podem regular esses processos durante o desenvolvimento pós-natal, provavelmente por ativação das vias de sinalização de MAPK e Src.
Title in English
The role of diet, transforming growth factor alpha and epidermal growth factor receptor in the cell proliferation and differentiation during the postnatal development of the gastric epithelium of rats.
Keywords in English
Animal stomach
Cell differentiation
Cell proliferaration
Epidermal growth factors receptors
Histology
Rats
Transforming growth factors alpha
Abstract in English
Early weaning (EW) causes changes in the gastric mucosa, including the increase in cell proliferation and Transforming Growth Factor (TGFa). In the present study, we evaluated the role of this peptide and its receptor EGFR in the control of the gastric growth. 15-d-old rats were divided into two groups: suckling (control) and EW, in which the pups were separated from the dam and fed with powdered chow. EW increased the number of EGFR-positive cells, accelerated the differentiation of mucous neck cells and augmented the expression of mucin 6. EGFR inhibition with AG1478 decreased cell proliferation and the number of mucous neck cells. Among the proteins involved on EGFR signaling pathways and cell cycle, we found that EW increased the levels of p-ERK1/2 and p-Src, but did not change p-Akt, p21 and p27. We suggest that the diet pattern influences proliferation and differentiation in the gastric epithelium, and the TGFa/EGFR can regulate these processes throughout the postnatal development, probably by activating MAPK and Src signaling pathways.
 
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Publishing Date
2009-12-08
 
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