Transforming Growth Factor beta 1 Increases p27 Levels via Synthesis and Degradation Mechanisms in the Hyperproliferative Gastric Epithelium in Rats

Autor(es)

Fiore, Ana P. Z. P. ^[1] ; Osaki, Luciana H. ^[1] ; Gama, Patricia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 9, n. 7 JUL 7 2014.
• Citações Web of Science: 0

Resumo

Throughout postnatal development, the gastric epithelium expresses Transforming Growth Factor beta1 (TGF beta 1), but it is also exposed to luminal peptides that are part of milk. During suckling period, fasting promotes the withdrawal of milk-born molecules while it stimulates gastric epithelial cell proliferation. Such response can be reversed by exogenous TGF beta 1, as it directly affects cell cycle through the regulation of p27 levels. We used fasting condition to induce the hyperproliferation of gastric epithelial cells in 14-day-old Wistar rats, and evaluated the effects of TGF beta 1 gavage on p27 expression, phosphorylation at threonine 187 (phospho-p27(Thr187)) and degradation. p27 protein level was reduced during fasting when compared to suckling counterparts, while phospho-p27(Thr187)/p27 ratio was increased. TGF beta 1 gavage reversed this response, which was confirmed through immunostaining. By using a neutralizing antibody against TGF beta 1, we found that it restored the p27 and phosphorylation levels detected during fasting, indicating the specific role of the growth factor. We noted that neither fasting nor TGF beta 1 changed p27 expression, but after cycloheximide administration, we observed that protein synthesis was influenced by TGF beta 1. Next, we evaluated the capacity of the gastric mucosa to degrade p27 and we recorded a higher concentration of the remaining protein in pups treated with TGF beta 1, suggesting augmented stability under this condition. Thus, we showed for the first time that luminal TGF beta 1 increased p27 levels in the rat gastric mucosa by up-regulating translation and reducing protein degradation. We concluded that such mechanisms might be used by rapidly proliferating cells to respond to milk-born TGF beta 1 and food restriction. (AU)

• Processo FAPESP: 08/05393-2 - Efeito do fator de crescimento transformante beta1 (TGFbeta1) sobre os níveis de p27kip1 na mucosa gástrica de ratos lactentes
• Beneficiário: Patrícia Gama
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/17415-3 - Desenvolvimento pós-natal da mucosa gástrica: papel da interação entre alimento, hormônios e fatores de crescimento
• Beneficiário: Patrícia Gama
• Modalidade de apoio: Auxílio à Pesquisa - Regular