Toll-like receptor-4 genotype influences the survival of cystic fibrosis mice

2010 ◽  
Vol 299 (2) ◽  
pp. G381-G390 ◽  
Author(s):  
Juan C. Canale-Zambrano ◽  
Meagan L. Auger ◽  
Christina K. Haston
Keyword(s):  
Cystic Fibrosis ◽  
Cell Proliferation ◽  
Double Mutant ◽  
Bacterial Load ◽  
Intestinal Disease ◽  
Intestinal Cell ◽  
Inflammatory Cell Infiltrate ◽  
Toll Like Receptor ◽  
Bacterial Classification ◽  
Crypt Cell Proliferation

Toll-like receptor (Tlr) 4 is a lipopolysaccharide (LPS) receptor that contributes to the regulation of intestinal cell homeostasis, a condition that is altered in the intestines of cystic fibrosis mice. Herein, we assessed whether Tlr4 genotype influences cystic fibrosis intestinal disease by producing and phenotyping 12-wk (adult)- and 4-day (neonate)-old mice derived from BALB cystic fibrosis transmembrane conductance regulator, Cftr+/tm1Uncand C.C3- Tlr4Lps-d/J ( Tlr4−/−), progenitors. Intestinal disease was assayed through mouse survival, crypt-villus axis (CVA) length, cell proliferation, bacterial load, bacterial classification, inflammatory cell infiltrate, and mucus content measures. Of the 77 Cftr−/−(CF) mice produced, only one Cftr/ Tlr4 double-mutant mouse lived to the age of 12 wk while the majority of the remainder succumbed at ∼4 days of age. The survival of CF Tlr4+/−mice exceeded that of both CF Tlr4+/+and Cftr/ Tlr4 double-mutant mice. Adult CF mice presented increased Tlr4 expression, CVA length, crypt cell proliferation, and bacterial load relative to non-CF mice, but no differences were detected in Tlr4+/−compared with Tlr4+/+CF mice. The double-mutant neonates did not differ from Tlr4+/+or Tlr4+/−CF mice by intestinal CVA length or bacterial load, but fewer Tlr4+/−CF neonates presented with luminal mucus obstruction in the distal ileum, and the intestinal mast cell increase of CF mice was not evident in double-mutant neonates. We conclude that Tlr4 deficiency reduces the survival, but does not alter the intestinal phenotypes, of extended CVA or increased bacterial load in BALB CF mice.

scholarly journals PSIV-22 Supplemental effects of dietary lysophospholipids in lactation diets on sow performance, milk composition, and intestinal health of piglets

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 174-175
Author(s):  
Kibeom Jang ◽  
Jerry Purvis ◽  
Sung Woo Kim
Keyword(s):  
Cell Proliferation ◽  
Block Design ◽  
Nutrient Utilization ◽  
Proliferation Rate ◽  
Crypt Cell ◽  
Intestinal Cell ◽  
Intestinal Health ◽  
Cell Proliferation Rate ◽  
Crypt Cell Proliferation ◽  
Supplemental Effects

Abstract Dietary lysophospholipids could enhance nutrient utilization through a structural change of enterocyte membrane with increasing permeability. The objective of this study was to determine supplemental effects of dietary lysophospholipids in lactation diets on sow performance, milk characteristics, and intestinal health of piglets. The 52 pregnant sows were allotted to 2 treatments in randomized complete block design with parity and BW as blocks at d 110 of pregnancy. The treatments were CON (no added lysophospholipids) and LPL (at 0.05% lysophospholipids; Lipidol-Ultra, Pathway Intermediates, Shrewsbury, UK). The lactation diets were formulated to meet or exceed nutrient requirements suggested by NRC (2012). Milk samples from 12 sows per treatment were collected to measure gross energy, protein, fat, fatty acid profile, and immunoglobulins (IgG and IgA) on d 1 and d 18 of lactation. Twelve piglets per treatment were euthanized on d 18 to collect tissues to measure tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), malondialdehyde, protein carbonyl, IgA, microbiota in jejunal and colonic mucosa, morphology and crypt cell proliferation rate in the jejunum. Data were analyzed using the MIXED procedure of SAS. Sows fed LPL tended to increase (P = 0.084) litter size (11.9 vs. 12.6) on d 18 of lactation and decrease (P = 0.079) ADFI (8.72 vs. 8.02 kg) during d 9 to d 18 of lactation. Sows fed LPL tended to increase (P = 0.092) IgG (1.14 vs. 1.94 g/L) in the milk. Sows fed LPL increased (P < 0.05) crypt cell proliferation rate (39.38 vs. 40.94%) in the jejunum. Supplementation of lysophospholipids in lactation diet did not affect proinflammatory cytokines, oxidative stress markers, and microbiota in jejunum and colon of piglets on d 18 of lactation. In conclusion, supplementation of dietary lysophopholipids improved productive performance and the intestinal cell proliferation of piglets with enhancing IgG concentration in the milk.

Cyste(i)ne stimulates intestinal cell proliferation independent of glutathione synthesis

2001 ◽  
Vol 120 (5) ◽  
pp. A502-A502
Author(s):  
T NODA ◽  
R IWAKIRI ◽  
K FUJIMOTO ◽  
T AW
Keyword(s):  
Cell Proliferation ◽  
Intestinal Cell ◽  
Glutathione Synthesis

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 < 0.05) and increased mucosal c-myc and Sox9 mRNA expression by 90 ± 20 and 376 ± 170%, respectively (P < 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 < 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 Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation

2015 ◽  
Vol 226 (3) ◽  
pp. 135-143 ◽  
Author(s):  
Tatiana Dorfman ◽  
Yulia Pollak ◽  
Rima Sohotnik ◽  
Arnold G Coran ◽  
Jacob Bejar ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Real Time ◽  
Real Time Pcr ◽  
Intestinal Epithelial Cell ◽  
Diabetic Rats ◽  
Male Rats ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation

The Wnt/β-catenin signaling cascade is implicated in the control of stem cell activity, cell proliferation, and cell survival of the gastrointestinal epithelium. Recent evidence indicates that the Wnt/β-catenin pathway is activated under diabetic conditions. The purpose of this study was to evaluate the role of Wnt/β-catenin signaling during diabetes-induced enteropathy in a rat model. Male rats were divided into three groups: control rats received injections of vehicle; diabetic rats received injections of one dose of streptozotocin (STZ); and diabetic–insulin rats received injections of STZ and were treated with insulin given subcutaneously at a dose of 1 U/kg twice daily. Rats were killed on day 7. Wnt/β-catenin-related genes and expression of proteins was determined using real-time PCR, western blotting, and immunohistochemistry. Among 13 genes identified by real-time PCR, seven genes were upregulated in diabetic rats compared with control animals including the target genes c-Myc and Tcf4. Diabetic rats also showed a significant increase in β-catenin protein compared with control animals. Treatment of diabetic rats attenuated the stimulating effect of diabetes on intestinal cell proliferation and Wnt/β-catenin signaling. In conclusion, enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation.

Is polyamine synthesis involved in the proliferative response of the intestinal epithelium to urogastrone-epidermal growth factor?

1989 ◽  
Vol 76 (6) ◽  
pp. 595-598 ◽  
Author(s):  
R. A. Goodlad ◽  
H. Gregory ◽  
N. A. Wright
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Proliferative Response ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Polyamine Synthesis ◽  
Proliferative Effect ◽  
Epidermal Growth

1. Intestinal epithelial cell proliferation was measured in rats maintained on total parenteral nutriton (TPN), in TPN rats given 300 μg of recombinant human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) day−1 kg−1, and in further groups given URO-EGF and difluoromethylornithine (DFMO), an inhibitor of the enzyme ornithine decarboxylase (ODC). 2. URO-EGF significantly increased intestinal cell proliferation throughout the gastrointestinal tract. The proliferative response of the colon was particularly pronounced. 3. DFMO reduced the proliferative effect of urogastrone in the stomach and small intestine. DFMO also reduced URO-EGF-stimulated intestinal cell proliferation in the colon, but to a lesser extent. 4. It is concluded that ODC is essential for effecting the proliferative response of the stomach and small intestine to URO-EGF, but this role may be less important in the colon.

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.

Impact of the cystic fibrosis mutation F508del-CFTR on renal cyst formation and growth

2012 ◽  
Vol 303 (8) ◽  
pp. F1176-F1186 ◽  
Author(s):  
Hongyu Li ◽  
Wanding Yang ◽  
Filipa Mendes ◽  
Margarida D. Amaral ◽  
David N. Sheppard
Keyword(s):  
Cystic Fibrosis ◽  
Cell Proliferation ◽  
Mdck Cells ◽  
Ussing Chamber ◽  
Cyst Formation ◽  
Transepithelial Resistance ◽  
Collagen Gels ◽  
Wild Type ◽  
Fluid Accumulation ◽  
The Impact

In autosomal dominant polycystic kidney disease (ADPKD), cystic fibrosis transmembrane conductance regulator (CFTR), the protein product of the gene defective in cystic fibrosis (CF), plays a crucial role in fluid accumulation, which promotes cyst swelling. Several studies have identified individuals afflicted by both ADPKD and CF. Two studies suggested that CF mutations might attenuate the severity of ADPKD, whereas a third found no evidence of a protective effect. In this study, we investigated the impact of the commonest CF mutation F508del-CFTR on the formation and growth of renal cysts. As a model system, we used Madin-Darby canine kidney (MDCK) epithelial cells engineered to express wild-type and F508del human CFTR. We grew MDCK cysts in collagen gels in the presence of the cAMP agonist forskolin and measured transepithelial resistance and Cl− secretion with the Ussing chamber technique and assayed cell proliferation using nonpolarized MDCK cells. When compared with untransfected MDCK cells, cells expressing wild-type CFTR generated substantial numbers of large cysts, which grew markedly over time. By contrast, MDCK cells expressing F508del-CFTR formed very few tiny cysts that failed to enlarge. Interestingly, treatment of F508del-CFTR cysts with the CFTR corrector VRT-325 and the CFTR corrector-potentiator VRT-532 increased the number, but not size, of F508del-CFTR cysts, possibly because VRT-325 inhibited strongly cell proliferation. Based on its effects on transepithelial resistance, Cl− secretion, and cell proliferation, we conclude that the F508del-CFTR mutation disrupts cyst formation and growth by perturbing strongly fluid accumulation within the cyst lumen without compromising epithelial integrity.

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