scholarly journals Bacillus Subtilis Expressing Epidermal Growth Factors Induces Intestinal Repair and Growth-Promoting in Mice

2021 ◽  
Author(s):  
Xiaoying Wu ◽  
Yue Li ◽  
Xiue Jin ◽  
Deshi Shi ◽  
xiliang Wang
Keyword(s):  
Cell Proliferation ◽  
Bacillus Subtilis ◽  
Luria Bertani ◽  
Feed Additive ◽  
Intestinal Cell ◽  
Intestinal Damage ◽  
Gastrointestinal Infections ◽  
Novel Therapy ◽  
Epidermal Growth ◽  
Intestinal Repair

Abstract Background: Probiotics are widely acknowledged for their pro-health attributes, but the efficacy of traditional probiotics is quite limited. This limitation can be overcome using a gene engineered to enhance the efficacy of existing probiotics. In this study, a strain of Bacillus subtilis (WB800) expressing the eukaryotic protein porcine epidermal growth factor (pEGF) was generated via genetic modification, and mice with intestinal injury were used as a model to evaluate the potential of this bioengineered probiotic in preventing or treating intestinal damage. Integration of the pEGF gene into the B. subtilis WB800 genome using an integrated expression vector pDG1730 resulted in stable expression of pEGF in B. subtilis (dubbed WB-EGF). Results: Female the Institute for Cancer Research (ICR) mice with intestinal damage received recombinant WB-EGF (1×108 –8×108 CFU/mL) for 10 d before collection of blood and intestinal tissues. Mice receiving WB-EGF had significantly higher body weight and longer intestinal villi than those of mice treated with Luria-Bertani (LB) broth or B. subtilis transformed with an empty vector. Cell proliferation assays confirmed enhanced intestinal cell proliferation in mice receiving WB-EGF. Conclusions: This study provides evidence that WB-EGF may have use as a novel therapy for early prevention or treatment of intestinal damage and for promoting intestinal development. The recombinant B. subtilis strain developed here can expected to provide protection when used as a feed additive in animals with gastrointestinal infections.

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.

INTRAVENOUS EPIDERMAL GROWTH FACTOR/UROGASTRONE INCREASES SMALL-INTESTINAL CELL PROLIFERATION IN CONGENITAL MICROVILLOUS ATROPHY

The Lancet ◽  
1985 ◽  
Vol 326 (8466) ◽  
pp. 1239-1240 ◽  
Author(s):  
J.A. Walker-Smith ◽  
A.D. Phillips ◽  
N. Walford ◽  
H. Gregory ◽  
J.D. Fitzgerald ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Intestinal Cell ◽  
Epidermal Growth ◽  
Small Intestinal

scholarly journals Human milk induces fetal small intestinal cell proliferation - involvement of a different tyrosine kinase signaling pathway from epidermal growth factor receptor

2004 ◽  
Vol 181 (3) ◽  
pp. 449-457 ◽  
Author(s):  
T Takeda ◽  
M Sakata ◽  
R Minekawa ◽  
T Yamamoto ◽  
M Hayashi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tyrosine Kinase ◽  
Human Milk ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Egf Receptor ◽  
Intestinal Cell ◽  
Epidermal Growth ◽  
Growth Promoting ◽  
Small Intestinal

Breast milk has non-nutritional protective effects on recipient infants. It has been speculated that bioactive substances present in human milk have important roles in protecting infants. However, the mechanisms by which such substances protect newborns are unclear. Therefore, we analyzed the growth-promoting activity of human milk and the intracellular signaling mechanism thereof using human fetal small intestinal (FHS 74 Int) cells. Epidermal growth factor (EGF) stimulated the proliferation of these cells. However, this stimulation was less effective than that of aqueous milk (5% vol/vol). The bioactivity of human milk was heat stable but protease sensitive. EGF receptor tyrosine kinase inhibitor did not repress the milk-induced growth-promoting effect on fetal small intestinal cells. Regarding the intracellular signaling pathway, the milk-induced cell proliferation pathway was tyrosine kinase dependent but was neither mitogen-activated protein (MAP) kinase nor phosphatidylinositol-3 (PI-3) kinase dependent. On the other hand, EGF-induced cell proliferation was tyrosine kinase, MAP kinase, and PI-3 kinase dependent. Rapid tyrosine phosphorylation of several intracellular proteins was detected after milk stimulation. Furthermore, the time course of phosphorylation induced by milk was different from that induced by EGF. The sizes of the proteins phosphorylated in response to milk were different from those of the Shc proteins phosphorylated in response to EGF. These results suggest that human milk induces fetal intestinal cell proliferation through a unique tyrosine kinase pathway different from the EGF receptor signaling pathway.

Effect of epidermal growth factor administration on intestinal cell proliferation, crypt fission and polyp formation in multiple intestinal neoplasia (Min) mice

2003 ◽  
Vol 105 (3) ◽  
pp. 323-330 ◽  
Author(s):  
O. BASHIR ◽  
A. J. FITZGERALD ◽  
J. BERLANGA-ACOSTA ◽  
R. J. PLAYFORD ◽  
R. A. GOODLAD
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Intestinal Cell ◽  
Polyp Size ◽  
Polyp Formation ◽  
Intestinal Neoplasia ◽  
Crypt Fission ◽  
Epidermal Growth

Recombinant epidermal growth factor (EGF) may be useful to treat severe ulcerative gastrointestinal injury. There is concern, however, that systemic use of this potent mitogen might increase tumour development and/or progression in susceptible subjects. We therefore examined the effect of chronic administration of systemic EGF to multiple intestinal neoplasia (Min) mice, who have a genetic defect in the adenomatous polyposis coli (APC) gene, leading to increased polyp development. Min mice (n=26) and wild-type littermates (n=26) received saline or EGF (223 μg of EGF/kg per day) for 4 weeks using subcutaneous osmotic mini-pumps. Cell proliferation and crypt fission were analysed using microdissection techniques and the number and size of polyps in the small and large intestines were determined. EGF increased wet weight and crypt cell proliferation rate by approx. 20% (all P<0.01 compared with the relevant control) in the small intestine and colon of both control and Min mice. In both groups, EGF reduced the colonic fission index by approx. 40% (P<0.01), but did not affect crypt fission in the small intestine. In Min mice, administration of EGF did not increase numbers of polyps or degree of dysplasia, but resulted in a 40% increase in the polyp size in the proximal intestine (P<0.02), but not in the remainder of the small intestine or colon. No polyps were found in control mice given EGF. EGF did not initiate polyp formation in control or Min mice. However, as polyp size is an important determinant for subsequent risk of malignant change in human colon cancer, further studies appear justified.

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

Computational Evaluation and In Vitro Validation of New Epidermal Growth Factor Receptor Inhibitors

2020 ◽  
Vol 20 (18) ◽  
pp. 1628-1639
Author(s):  
Sergi Gómez-Ganau ◽  
Josefa Castillo ◽  
Andrés Cervantes ◽  
Jesus Vicente de Julián-Ortiz ◽  
Rafael Gozalbes
Keyword(s):  
Cell Proliferation ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Binding Affinity ◽  
Cell Lines ◽  
Growth Factor Receptor ◽  
Significant Activity ◽  
Epidermal Growth

Background: The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein that acts as a receptor of extracellular protein ligands of the epidermal growth factor (EGF/ErbB) family. It has been shown that EGFR is overexpressed by many tumours and correlates with poor prognosis. Therefore, EGFR can be considered as a very interesting therapeutic target for the treatment of a large variety of cancers such as lung, ovarian, endometrial, gastric, bladder and breast cancers, cervical adenocarcinoma, malignant melanoma and glioblastoma. Methods: We have followed a structure-based virtual screening (SBVS) procedure with a library composed of several commercial collections of chemicals (615,462 compounds in total) and the 3D structure of EGFR obtained from the Protein Data Bank (PDB code: 1M17). The docking results from this campaign were then ranked according to the theoretical binding affinity of these molecules to EGFR, and compared with the binding affinity of erlotinib, a well-known EGFR inhibitor. A total of 23 top-rated commercial compounds displaying potential binding affinities similar or even better than erlotinib were selected for experimental evaluation. In vitro assays in different cell lines were performed. A preliminary test was carried out with a simple and standard quick cell proliferation assay kit, and six compounds showed significant activity when compared to positive control. Then, viability and cell proliferation of these compounds were further tested using a protocol based on propidium iodide (PI) and flow cytometry in HCT116, Caco-2 and H358 cell lines. Results: The whole six compounds displayed good effects when compared with erlotinib at 30 μM. When reducing the concentration to 10μM, the activity of the 6 compounds depends on the cell line used: the six compounds showed inhibitory activity with HCT116, two compounds showed inhibition with Caco-2, and three compounds showed inhibitory effects with H358. At 2 μM, one compound showed inhibiting effects close to those from erlotinib. Conclusion: Therefore, these compounds could be considered as potential primary hits, acting as promising starting points to expand the therapeutic options against a wide range of cancers.

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