Neurotensin Augments Intestinal Regeneration After Small Bowel Resection in Rats

Izukura, M; Evers, B. Mark; Parekh, Dilipkumar; Yoshinaga, Keigo; Uchida, Tatsuo; Townsend, Courtney M.; Thompson, James C.

doi:10.1097/00000658-199205000-00015

Cited by 59 publications

(27 citation statements)

References 27 publications

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“…Assessment of morphological changes can be used in the diagnosis and assessment of intestinal pathology (Isukura et al, 1992). In this study, no significant changes occurred in the gross morphometry and histology of the small and large intestines, other than in the caecum.…”

mentioning

confidence: 66%

The Effects of Crude Aqueous and Alcohol Extracts of <em>Aloe Vera</em> on Growth and Abdominal Viscera of Suckling Rats

Beya¹,

Davidson²,

Erlwanger³

2012

Afr. J. Trad. Compl. Alt. Med.

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The gastrointestinal tract of neonates is sensitive to dietary manipulations. When nursing mothers use Aloe vera, their babies are at risk of indirect exposure to Aloe vera via breast feeding or directly as health supplements. The effects of orally administered extracts of Aloe vera in unweaned rats were investigated. Six day old Sprague-Dawley rats were gavaged with aqueous or alcohol extracts of Aloe vera (low dose 50mg. kg -1 or high dose 500mg. kg) daily for eight days. All data were expressed as mean ± SD and analyzed by one way ANOVA. Pups receiving high doses of either extract had a significantly higher body mass gain than the group receiving lower dose (p < 0.05). Tibial length was significantly increased in the high dose aqueous extract group (15-26 %). The differences in growth could not be attributed to circulating insulin-like growth factor-1 as the levels were not significantly different. The caecum was significantly enlarged in the rats that received the high doses of both extracts. Although, there was no significant difference in the non-fasting plasma concentration of glucose and triglycerides, the hepatic lipid and glycogen content were significantly higher (p < 0.001) for the high dose aqueous extract group. The plasma alanine transaminase was not affected by the treatments, however the high doses of the extracts significantly increased plasma alkaline phosphatase activity. Short term administration of Aloe vera extracts resulted in growth promotion, enhanced hepatic storage of metabolic substrates, increased ALP possibly in relation to bone growth and caused hypertrophy of the caecum of neonatal rats. These effects need to be explored further to enhance animal production and health.

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mentioning

confidence: 66%

The Effects of Crude Aqueous and Alcohol Extracts of <em>Aloe Vera</em> on Growth and Abdominal Viscera of Suckling Rats

Beya¹,

Davidson²,

Erlwanger³

2012

Afr. J. Trad. Compl. Alt. Med.

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“…NT modulates motility in the stomach, small bowel, and colon (3)(4)(5) and stimulates secretion in the dog jejunum (6) and human colonic mucosa (7,8). NT also stimulates growth and regeneration of the intestinal mucosa (9,10) and has been implicated in the pathophysiology of colon cancer (11,12).…”

Section: Neurotensin (Nt)mentioning

confidence: 99%

Insulin-like Growth Factor-1 Receptor Transactivation Modulates the Inflammatory and Proliferative Responses of Neurotensin in Human Colonic Epithelial Cells

Zhao

Bakirtzi

Zhan

et al. 2011

Journal of Biological Chemistry

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sion. This is the first report to indicate that NT transactivates IGF-1R and that this response is linked to Akt phosphorylation and NF-B activation, contributing to both pro-inflammatory and tissue repair signaling pathways in response to NT in colonic epithelial cells. We propose that IGF-1R activation represents a previously unrecognized key pathway involved in the mechanisms by which NT and NTR1 modulate colonic inflammation and inflammatory bowel disease. Neurotensin (NT)4 is a 13-amino acid neuropeptide initially isolated from the bovine hypothalamus by Carraway and Leeman (1) and is highly expressed in the gastrointestinal tract (2). NT modulates motility in the stomach, small bowel, and colon (3-5) and stimulates secretion in the dog jejunum (6) and human colonic mucosa (7,8). NT also stimulates growth and regeneration of the intestinal mucosa (9, 10) and has been implicated in the pathophysiology of colon cancer (11,12).Two G-protein-coupled receptors (GPCRs) have been described for NT: a high-affinity (NTR1) and a low-affinity (NTR2) receptor (13). A third, non-GPCR has also been identified (14). Several studies underlined the importance of NTR1 in several intestinal pathologic conditions. Administration of the specific NTR1 antagonist SR 48692 to rats inhibits colonic responses to stress (15, 16) and reduces colonic secretion and inflammation mediated by Clostridium difficile toxin A (17). Increased NTR1 expression is evident in the colonic mucosa during the course of acute colitis mediated by toxin A (17), in the colons of mice with experimental colitis (18), and in humans with inflammatory bowel disease (18). In a recent study, we also showed that involvement of NT in colonic inflammation may include direct stimulation of pro-inflammatory chemoattractant IL-8 transcription in colonic epithelial cells (19).NT stimulates several intracellular signaling events, as shown in human colonic and pancreatic cell lines expressing endogenous NTR1 (20, 21). These include increased intracellular calcium release (22, 23) and activation of the MAPK family member ERK1/2 in pancreatic MIA PaCa-2 cells (24), transformed colonic adenocarcinoma HT29 cells (24), and non-transformed human colonic epithelial NCM460 cells (19). Our recent studies indicate that NT also activates the NF-B pathway (19) and the Rho family of small GTPases (25,26). Two previous studies showed that pretreatment with PKC inhibitors reduces NT-induced ERK1/2 activation in CHO cells overexpressing NTR1 (24) and in pancreatic carcinoma PANC-1 cells expressing endogenous NTR1 (27). In contrast, our laboratory and Hassan et al. have found that EGF receptor (EGFR) transactivation is involved in NT-in-

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“…2 In the small intestine, NT is synthesized and secreted by specific mucosal endocrine cells in response to several different stimuli. 3,4 NT modulates GI tract motility, [5][6][7] stimulates intestinal secretion, 8,9 stimulates growth and regeneration of the intestinal mucosa, 10,11 and has been implicated in the pathophysiology of colon cancer. 12,13 Two G-protein coupled receptors have been described for NT; a high affinity (NTR1) and a low affinity (NTR2) receptor 14 in addition to a third, non G-protein coupled receptor.…”

mentioning

confidence: 99%

Neurotensin stimulates expression of early growth response gene‐1 and EGF receptor through MAP kinase activation in human colonic epithelial cells

Zhao¹,

Zhan²,

Zeng³

et al. 2007

Intl Journal of Cancer

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Neurotensin (NT) is a highly expressed gastrointestinal (GI) neuropeptide, which modulates GI motility, secretion and cell growth as well as intestinal inflammation. Since EGF receptor is highly expressed in human colon cancer cells, we sought to examine whether NT stimulation contributes to the EGFR overexpression using nontransformed colonocyte NCM460 cells. The results show that NT treatment caused a significant increase in EGFR protein expression and gene transcription. Pretreatment with MAP kinase pathway inhibitor PD98059 blocked NT-induced EGFR expression. As the EGFR promoter has a functional Egr-1 site, previously shown to mediate its transcription in response to hypoxia, we examined the role of Egr-1 in the NT response. We first show that NT stimulated Egr-1 expression, which can be inhibited by PD98059. We also determined whether NT increases Egr-1 binding to its site within the EGFR promoter. The data indicate that NT enhanced the amount of Egr-1 binding to the EGFR Egr-1 site and that this binding was significantly decreased by PD98059. To verify that Egr-1 mediated NT-induced EGFR transcription, Egr-1 siRNA was used to knock down its expression. The data show that transfection of Egr-1 siRNA significantly inhibited NT-stimulated EGFR transcription. Together, our results suggest that NT can stimulate MAP kinase-mediated Egr-1 and EGFR gene expression in human colonocytes. Our results may be relevant to the mechanisms by which NT participates in the development of colon cancer. ' 2007 Wiley-Liss, Inc.Key words: neurotensin; early growth response gene-1; EGF receptor Neurotensin (NT) is a 13 amino acid neuropeptide that was initially isolated from bovine hypothalamus by Carraway and Leeman.1 Subsequently, it was found that its highest expression is localized in the gastrointestinal (GI) tract.2 In the small intestine, NT is synthesized and secreted by specific mucosal endocrine cells in response to several different stimuli.3,4 NT modulates GI tract motility, 5-7 stimulates intestinal secretion, 8,9 stimulates growth and regeneration of the intestinal mucosa, 10,11 and has been implicated in the pathophysiology of colon cancer.12,13 Two G-protein coupled receptors have been described for NT; a high affinity (NTR1) and a low affinity (NTR2) receptor 14 in addition to a third, non G-protein coupled receptor. 15 Several studies underlined the importance of NTR1 in several intestinal pathologic conditions, which include immobilization stress responses, 16Clostridium difficile toxin A-mediated acute colitis 17 and intestinal wound healing during chronic inflammation.18 Increased NTR1 expression is evident in the colonic mucosa during these conditions [16][17][18] as well as in colonic carcinoma and derived cell lines. 19NT stimulates several intracellular signaling events as shown in human colonic and pancreatic cell lines expressing endogenous NTR1. 20,21 These include increased intracellular calcium release 22,23 and activation of the mitogen activating protein kinase (MAPK) family member ERK1/2. 24,25 N...

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Neurotensin Augments Intestinal Regeneration After Small Bowel Resection in Rats

Cited by 59 publications

References 27 publications

The Effects of Crude Aqueous and Alcohol Extracts of <em>Aloe Vera</em> on Growth and Abdominal Viscera of Suckling Rats

The Effects of Crude Aqueous and Alcohol Extracts of <em>Aloe Vera</em> on Growth and Abdominal Viscera of Suckling Rats

Insulin-like Growth Factor-1 Receptor Transactivation Modulates the Inflammatory and Proliferative Responses of Neurotensin in Human Colonic Epithelial Cells

Neurotensin stimulates expression of early growth response gene‐1 and EGF receptor through MAP kinase activation in human colonic epithelial cells

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