Polyamines and intestinal growth--increased polyamine biosynthesis after jejunectomy

1983 ◽  
Vol 245 (5) ◽  
pp. G656-G660 ◽  
Author(s):  
G. D. Luk ◽  
S. B. Baylin
Keyword(s):  
Cell Proliferation ◽  
Intestinal Adaptation ◽  
Intestinal Resection ◽  
Crypt Cell ◽  
Mucosal Cell ◽  
Ileal Mucosa ◽  
Cell Hyperplasia ◽  
Polyamine Biosynthesis ◽  
Crypt Cell Proliferation ◽  
Mucosal Cell Proliferation

Transient increases in the activities of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAM-DC), key enzymes in polyamine biosynthesis, may be critical to initiation of cell growth. We now report that such increases in ODC (X170) and SAM-DC (X83) activities, and their synthetic products putrescine (X4) and spermidine (X2), occur in rat ileal mucosa between days 1 and 4 after 50% intestinal resection. This is the time period of initiation of mucosal cell hyperplasia in intestinal adaptation after resection and is characterized by increased mucosal cell proliferation, as measured morphologically and biochemically. Intestinal weight increased by 76% and mucosal thickness by 48%. Mucosal DNA content increased by 67% and mucosal DNA synthesis by 104%. Increased intestinal crypt cell proliferation was manifested by a 120% increase in labeling per crypt and a 152% increase in crypt cell production rate (CCPR). The increase in ODC activity was closely associated with the increases in CCPR and rate of villus lengthening. Rates of mucosal cell proliferation, as measured by CCPR, and villus and crypt lengthening were significantly correlated with ODC activity (r = 0.97, 0.98, and 0.94, respectively; P less than 0.01 for all). Our results indicate that the increase in ODC activity, SAM-DC activity, and polyamine biosynthesis is closely associated with the process of adaptive postresectional crypt cell proliferation.

Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome

2005 ◽  
Vol 288 (3) ◽  
pp. G431-G438 ◽  
Author(s):  
G. R. Martin ◽  
L. E. Wallace ◽  
B. Hartmann ◽  
J. J. Holst ◽  
L. Demchyshyn ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Time Course ◽  
Intestinal Adaptation ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Crypt Cell ◽  
Crypt Cell Proliferation ◽  
Proximal Intestine ◽  
The Relationship ◽  
Over Time

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine peptide that is released in response to luminal nutrients and has unique trophic actions in the gastrointestinal tract. These features suggest GLP-2 may be important in controlling intestinal adaptation. We examined the relationship over time of GLP-2 production and adaptation to intestinal resection, the effects of resection-induced malabsorption on GLP-2 production, and the correlation of endogenous serum GLP-2 levels with adaptation as measured by crypt-cell proliferation (CCP). We initially examined the effect of nutrient malabsorption, induced by a 90% resection of the proximal intestine studied on day 4, on the time course and levels of GLP-2 release. Secondly, the degree of malabsorption was varied by performing intestinal transection or 50, 75, or 90% resection of proximal small intestine. Finally, the relationship of GLP-2 levels over time with adaptation to a 90% resection was examined by determining GLP-2 levels on days 7, 14, and 28, and correlating this with intestinal adaptation, as assessed by morphology and CCP rate. A 90% resection significantly increased basal and postprandial GLP-2 levels, with a net increase in nutrient-stimulated exposure over 90 min; GLP-2 exposure (integrated levels vs. time) increased 12.7-fold in resected animals ( P < 0.001). Basal and postprandial GLP-2 levels significantly correlated with the magnitude of intestinal resection ( r2 = 0.71; P < 0.001), CCP ( r2 = 0.48; P < 0.005), and nutrient malabsorption (protein, P < 0.001; fat, P < 0.005). The increase in CCP was maintained to 28 days after small bowel resection and was associated with an ongoing elevation in GLP-2 release. These findings suggest that GLP-2 is important in initiating and maintaining the small intestinal adaptive response to resection.

Increased apoptosis and accelerated epithelial migration following inhibition of hedgehog signaling in adaptive small bowel postresection

2006 ◽  
Vol 290 (6) ◽  
pp. G1280-G1288 ◽  
Author(s):  
Yuzhu Tang ◽  
Elzbieta A. Swietlicki ◽  
ShuJun Jiang ◽  
Kim K. Buhman ◽  
Nicholas O. Davidson ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Small Bowel ◽  
Surface Area ◽  
Intestinal Adaptation ◽  
Critical Role ◽  
Intestinal Resection ◽  
Crypt Cell ◽  
Epithelial Migration ◽  
Crypt Cell Proliferation ◽  
Hh Signaling

The intestinal epithelium undergoes a marked adaptive response following loss of functional small bowel surface area characterized by increased crypt cell proliferation and increased enterocyte migration from crypt to villus tip, resulting in villus hyperplasia and enhanced nutrient absorption. Hedgehog (Hh) signaling plays a critical role in regulating epithelial-mesenchymal interactions during morphogenesis of the embryonic intestine. Our previous studies showed that blocking Hh signaling in neonatal mice results in increased small intestinal epithelial crypt cell proliferation and altered enterocyte fat absorption and morphology. Hh family members are also expressed in the adult intestine, but their role in the mature small bowel is unclear. With the use of a model of intestinal adaptation following partial small bowel resection, the role of Hh signaling in the adult gut was examined by determining the effects of blocking Hh signaling on the regenerative response following loss of functional surface area. Hh-inactivating monoclonal antibodies or control antibodies were administered to mice that sustained a 50% intestinal resection. mRNA analyses of the preoperative ileum by quantitative real-time PCR revealed that Indian hedgehog was the most abundant Hh family member. The Hh receptor Patched was more abundant than Patched 2. Analyses of downstream targets of Hh signaling demonstrated that Gli3 was twofold more abundant than Gli1 and Gli2 and that bone morphogenetic protein ( BMP) 2 was most highly expressed compared with BMP1, - 4, and - 7. Following intestinal resection, the expression of Hh, Patched, Gli, and most BMP genes was markedly downregulated in the remnant ileum, and, in anti-Hh antibody-treated mice, expression of Patched 2 and Gli 1 was further suppressed. In Hh antibody-treated mice following resection, the enterocyte migration rate from crypt to villus tip was increased, and by 2 wk postoperation, apoptosis was increased in the adaptive gut. However, crypt cell proliferation, villus height, and crypt depth were not augmented. These data indicate that Hh signaling plays a role in adult gut epithelial homeostasis by regulating epithelial cell migration from crypt to villus tip and by enhancing apoptosis.

Vitamin A deficiency inhibits intestinal adaptation by modulating apoptosis, proliferation, and enterocyte migration

2003 ◽  
Vol 285 (2) ◽  
pp. G424-G432 ◽  
Author(s):  
Deborah A. Swartz-Basile ◽  
Lihua Wang ◽  
Yuzhu Tang ◽  
Henry A. Pitt ◽  
Deborah C. Rubin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Small Bowel ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Intestinal Adaptation ◽  
Collagen Iv ◽  
Crypt Cell ◽  
Migration Rates ◽  
Crypt Cell Proliferation ◽  
Extracellular Matrix Components

In a prior study, vitamin A-deficient rats subjected to submassive small bowel resections did not mount a normal intestinal adaptive response by 10 days postoperatively, although adaptive increases in crypt cell proliferation were not attenuated and there were no differences in apoptotic indexes. The present study was designed to address the mechanisms by which vitamin A status effects adaptation by analyzing proliferation, apoptosis, and enterocyte migration in the early postoperative period (16 and 48 h) in vitamin A-sufficient, -deficient, and partially replenished sham-resected and resected rats. At 16 h postresection, apoptosis was significantly greater in the remnant ileum of resected vitamin A-deficient rats compared with the sufficient controls. Crypt cell proliferation was increased by resection in all dietary groups at both timepoints. However, at 48 h postresection, proliferation was significantly decreased in the vitamin A-deficient and partially replenished rats. By 48 h after resection, vitamin A deficiency also reduced enterocyte migration rates by 44%. This occurred in conjunction with decreased immunoreactive collagen IV at 48 h and 10 days postoperation. Laminin expression was also reduced by deficiency at 10 days postresection, whereas fibronectin and pancadherin were unchanged at 48 h and 10 days. These studies indicate that vitamin A deficiency inhibits intestinal adaptation following partial small bowel resection by reducing crypt cell proliferation, by enhancing early crypt cell apoptosis, and by markedly reducing enterocyte migration rates, which may be related to changes in the expression of collagen IV and other extracellular matrix components.

Polyamines and intestinal growth: absolute requirement for ODC activity in adaptation during lactation

1984 ◽  
Vol 247 (5) ◽  
pp. G553-G557 ◽  
Author(s):  
P. Yang ◽  
S. B. Baylin ◽  
G. D. Luk
Keyword(s):  
Cell Proliferation ◽  
Intestinal Adaptation ◽  
Specific Inhibitor ◽  
Maximal Increase ◽  
Polyamine Biosynthesis ◽  
Cell Proliferation And Differentiation ◽  
Marked Diminution ◽  
Absolute Requirement ◽  
Crypt Cell Proliferation ◽  
Proliferation And Differentiation

Ornithine decarboxylase (ODC), through the regulation of polyamine biosynthesis, is important in cell proliferation and differentiation. We followed intestinal mucosal ODC activity in lactating Lewis rats and correlated the ODC levels with the characteristic small intestinal adaptive changes accompanying lactation. During the first 14 days of lactation, mucosal ODC activity increased, with the maximal increase on day 5 corresponding to the time of maximal morphological intestinal adaptation. In animals given the specific inhibitor of ODC, alpha-difluoromethylornithine (DFMO), intestinal mucosal ODC activity was inhibited, and intestinal adaptation was suppressed, with marked diminution of the adaptive increase in mucosal weight and thickness especially in crypt depth. Our results suggest that ODC activity plays an essential role in mucosal hyperplasia during the intestinal adaptation accompanying lactation, possibly through the stimulation of crypt cell proliferation.

Reduction of mucosal crypt cell proliferation in patients with colorectal adenomatous polyps by dietary calcium supplementation

1992 ◽  
Vol 79 (6) ◽  
pp. 581-583 ◽  
Author(s):  
G. H. Barsoum ◽  
C. Hendrickse ◽  
M. C. Winslet ◽  
D. Youngs ◽  
I. A. Donovan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Calcium Supplementation ◽  
Dietary Calcium ◽  
Crypt Cell ◽  
Adenomatous Polyps ◽  
Crypt Cell Proliferation

scholarly journals Glucagon-Like Peptide-2 Activates β-Catenin Signaling in the Mouse Intestinal Crypt: Role of Insulin-Like Growth Factor-I

Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 291-301 ◽  
Author(s):  
Philip E. Dubé ◽  
Katherine J. Rowland ◽  
Patricia L. Brubaker
Keyword(s):  
Cell Proliferation ◽  
Nuclear Translocation ◽  
Glycogen Synthase ◽  
Crypt Cell ◽  
Acute Administration ◽  
Intestinal Crypt ◽  
Crypt Cell Proliferation ◽  
Igf I ◽  
Glucagon Like Peptide ◽  
Crypt Cells

Chronic administration of glucagon-like peptide-2 (GLP-2) induces intestinal growth and crypt cell proliferation through an indirect mechanism requiring IGF-I. However, the intracellular pathways through which IGF-I mediates GLP-2-induced epithelial tropic signaling remain undefined. Because β-catenin and Akt are important regulators of crypt cell proliferation, we hypothesized that GLP-2 activates these signaling pathways through an IGF-I-dependent mechanism. In this study, fasted mice were administered Gly2-GLP-2 or LR3-IGF-I (positive control) for 0.5–4 h. Nuclear translocation of β-catenin in non-Paneth crypt cells was assessed by immunohistochemistry and expression of its downstream proliferative markers, c-myc and Sox9, by quantitative RT-PCR. Akt phosphorylation and activation of its targets, glycogen synthase kinase-3β and caspase-3, were determined by Western blot. IGF-I receptor (IGF-IR) and IGF-I signaling were blocked by preadministration of NVP-AEW541 and through the use of IGF-I knockout mice, respectively. We found that GLP-2 increased β-catenin nuclear translocation in non-Paneth crypt cells by 72 ± 17% (P &lt; 0.05) and increased mucosal c-myc and Sox9 mRNA expression by 90 ± 20 and 376 ± 170%, respectively (P &lt; 0.05–0.01), with similar results observed with IGF-I. This effect of GLP-2 was prevented by blocking the IGF-IR as well as ablation of IGF-I signaling. GLP-2 also produced a time- and dose-dependent activation of Akt in the intestinal mucosa (P &lt; 0.01), most notably in the epithelium. This action was reduced by IGF-IR inhibition but not IGF-I knockout. We concluded that acute administration of GLP-2 activates β-catenin and proliferative signaling in non-Paneth murine intestinal crypt cells as well as Akt signaling in the mucosa. However, IGF-I is required only for the GLP-2-induced alterations in β-catenin.

scholarly journals Localization and significance of pp55, a gastric mucosal membrane protein with tyrosine kinase activity

1998 ◽  
Vol 274 (5) ◽  
pp. G863-G870 ◽  
Author(s):  
Adhip P. N. Majumdar ◽  
James R. Goldenring
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Mucosal Cell ◽  
Mucous Cells ◽  
Tyrosine Kinase Activity ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mucosal Cell Proliferation

In Fischer 344 rats, induction of gastric mucosal proliferative activity, whether the result of aging or injury or occurring after administration of epidermal growth factor, gastrin, or bombesin, is associated with a rise in tyrosine kinase activity and tyrosine phosphorylation of several mucosal proteins, including a protein with a molecular mass of 53–55 kDa. We hypothesized that this phosphotyrosine membrane protein (referred to as pp55) may play a role in regulating gastric mucosal cell proliferation and differentiation. Purification and subsequent immunoprecipitation studies now show that pp55 is a tyrosine kinase. In addition, the enzyme activity in the gastric mucosa is found to be fourfold higher in aged rats than in young rats. Incubation of gastric mucosal membranes with transforming growth factor-α (2 × 10−8 M) stimulates tyrosine kinase activity of pp55. Immuolocalization studies reveal that pp55 immunoreactivity is predominantly present in mucous cells that are located just above the proliferative zone and spasmolytic peptide-immunoreactive mucous neck cells. Tyrosine kinase activity as well as expression of pp55 are also greatly increased in the gastric mucosa after hypertonic saline-induced injury, a condition that results in stimulation of surface mucosal cell proliferation and differentiation. Our current data suggest that pp55 is a tyrosine kinase, likely localized to pre-surface cells. The presence of pp55 in pre-surface mucous cells and the expression and tyrosine kinase activity of this protein, which can be stimulated during mucosal cell proliferation and differentiation, strongly suggest a role for pp55 in differentiation of gastric surface mucous cells.

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