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Suppressor of cytokine signaling-2 limits intestinal growth and enterotrophic actions of IGF-I in vivo.
Michaylira, Carmen Z; Simmons, James G; Ramocki, Nicole M; Scull, Brooks P; McNaughton, Kirk K; Fuller, C Randall; Lund, P Kay.
Afiliação
  • Michaylira CZ; CB#7545, Dept. of Cell and Molecular Physiology, Univ. of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7545, USA.
Am J Physiol Gastrointest Liver Physiol ; 291(3): G472-81, 2006 Sep.
Article em En | MEDLINE | ID: mdl-16574995
ABSTRACT
Suppressors of cytokine signaling (SOCS) typically limit cytokine receptor signaling via the JAK-STAT pathway. Considerable evidence demonstrates that SOCS2 limits growth hormone (GH) action on body and organ growth. Biochemical evidence that SOCS2 binds to the IGF-I receptor (IGF-IR) supports the novel possibility that SOCS2 limits IGF-I action. The current study tested the hypothesis that SOCS2 normally limits basal or IGF-I-induced intestinal growth and limits IGF-IR signaling in intestinal epithelial cells. Intestinal growth was assessed in mice homozygous for SOCS2 gene deletion (SOCS2 null) and wild-type (WT) littermates at different ages and in response to infused IGF-I or vehicle or EGF and vehicle. The effects of SOCS2 on IGF-IR signaling were examined in ex vivo cultures of SOCS2 null and WT intestine and Caco-2 cells. Compared with WT, SOCS2 null mice showed significantly enhanced small intestine and colon growth, mucosal mass, and crypt cell proliferation and decreases in radiation-induced crypt apoptosis in jejunum. SOCS2 null mice showed significantly greater growth responses to IGF-I in small intestine and colon. IGF-I-stimulated activation of IGF-IR and downstream signaling intermediates were enhanced in the intestine of SOCS2 null mice and were decreased by SOCS2 overexpression in Caco-2 cells. SOCS2 bound directly to the endogenous IGF-IR in Caco-2 cells. The intestine of SOCS2 null mice also showed enhanced growth responses to infused EGF. We conclude that SOCS2 normally limits basal and IGF-I- and EGF-induced intestinal growth in vivo and has novel inhibitory effects on the IGF-IR tyrosine kinase pathway in intestinal epithelial cells.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Fator de Crescimento Insulin-Like I / Proteínas Supressoras da Sinalização de Citocina / Mucosa Intestinal / Intestinos Limite: Animals Idioma: En Revista: Am J Physiol Gastrointest Liver Physiol Assunto da revista: FISIOLOGIA / GASTROENTEROLOGIA Ano de publicação: 2006 Tipo de documento: Article País de afiliação: Estados Unidos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Fator de Crescimento Insulin-Like I / Proteínas Supressoras da Sinalização de Citocina / Mucosa Intestinal / Intestinos Limite: Animals Idioma: En Revista: Am J Physiol Gastrointest Liver Physiol Assunto da revista: FISIOLOGIA / GASTROENTEROLOGIA Ano de publicação: 2006 Tipo de documento: Article País de afiliação: Estados Unidos