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

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 ce...

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Bibliographic Details
Published in:PloS one 2014-07, Vol.9 (7)
Main Authors: Fiore, Ana P. Z. P, Osaki, Luciana H, Gama, Patricia
Format: Article
Language:English
Subjects:
Epithelium
Milk
Protein synthesis
Proteolysis
Statistics
Transforming growth factors
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Summary: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.sup.Thr187) and degradation. p27 protein level was reduced during fasting when compared to suckling counterparts, while phospho-p27.sup.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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0101965