Glutamine and alanyl-glutamine promote crypt expansion and mTOR signaling in murine enteroids.
Am J Physiol Gastrointest Liver Physiol
; 308(10): G831-9, 2015 May 15.
Article
em En
| MEDLINE
| ID: mdl-25792564
ABSTRACT
L-glutamine (Gln) is a key metabolic fuel for intestinal epithelial cell proliferation and survival and may be conditionally essential for gut homeostasis during catabolic states. We show that L-alanyl-L-glutamine (Ala-Gln), a stable Gln dipeptide, protects mice against jejunal crypt depletion in the setting of dietary protein and fat deficiency. Separately, we show that murine crypt cultures (enteroids) derived from the jejunum require Gln or Ala-Gln for maximal expansion. Once expanded, enteroids deprived of Gln display a gradual atrophy of cryptlike domains, with decreased epithelial proliferation, but stable proportions of Paneth and goblet cell differentiation, at 24 h. Replenishment of enteroid medium with Gln selectively activates mammalian target of rapamycin (mTOR) signaling pathways, rescues proliferation, and promotes crypt regeneration. Gln deprivation beyond 48 h leads to destabilization of enteroids but persistence of EGFP-Lgr5-positive intestinal stem cells with the capacity to regenerate enteroids upon Gln rescue. Collectively, these findings indicate that Gln deprivation induces a reversible quiescence of intestinal stem cells and provides new insights into nutritional regulation of intestinal epithelial homeostasis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Dipeptídeos
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Serina-Treonina Quinases TOR
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Glutamina
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Mucosa Intestinal
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Gastrointest Liver Physiol
Assunto da revista:
FISIOLOGIA
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GASTROENTEROLOGIA
Ano de publicação:
2015
Tipo de documento:
Article