Microbial recognition regulates intestinal epithelial growth in homeostasis and disease

Sprague-Dawley rats that had been subjected 2 months previously to partial resection (10 per cent) of the small intestine and an equal number of control rats were injected with tritiated thymidine and sacrificed at intervals during the subsequent 16 hours. Segments of duodenum, jejunum and ileum were prestained by the Feulgen technique and radioautographed. The proportion of crypt cells bearing labeled nuclei, the percentage of labeled crypt cells in mitosis and the appearance of labeled crypt cells on the villi were determined. Comparison of control and resected rats showed that (a) the proportion of intestinal crypt cells incorporating thymidine was considerably greater and uniformly high throughout the shortened intestine, (b) the life cycle of crypt cells was slightly reduced, and was uniform throughout the shortened intestine, and (c) the time during which cells were retained in crypts was markedly reduced. On the basis of persistent, generalized increase in the production of crypt cells, and on prior evidence that the epithelial cells of shortened intestine continue to have a brief life span and evidence of metabolic immaturity, the existence of a humoral factor, tentatively called "intestinal epithelial growth hormone," is postulated.

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Enteroid Monolayers Reveal an Autonomous WNT and BMP Circuit Controlling Intestinal Epithelial Growth and Organization

Developmental Cell ◽

10.1016/j.devcel.2018.01.024 ◽

2018 ◽

Vol 44 (5) ◽

pp. 624-633.e4 ◽

Cited By ~ 47

Author(s):

Curtis A. Thorne ◽

Ina W. Chen ◽

Laura E. Sanman ◽

Melanie H. Cobb ◽

Lani F. Wu ◽

...

Keyword(s):

Intestinal Epithelial ◽

Epithelial Growth

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W1566 Roles of Amphiregulin in Intestinal Epithelial Growth

Gastroenterology ◽

10.1016/s0016-5085(09)63191-7 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-693

Author(s):

Jinyi Shao ◽

Hongmiao Sheng

Keyword(s):

Intestinal Epithelial ◽

Epithelial Growth

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Hepatocyte growth factor region-specifically stimulates gastro-intestinal epithelial growth in primary culture

Gastroenterology ◽

10.1016/0016-5085(95)27281-x ◽

1995 ◽

Vol 108 (4) ◽

pp. A742

Author(s):

M. Oka ◽

M. Ichinose ◽

S. Tsukada ◽

Y. Matsubara ◽

N. Kakei ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Primary Culture ◽

Intestinal Epithelial ◽

Hepatocyte Growth ◽

Epithelial Growth

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Planar Enteroids Reveal an Autonomous WNT And BMP Circuit Controlling Intestinal Epithelial Growth and Organization

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.659.14 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Curtis A. Thorne ◽

Ina W. Chen ◽

Laura E. Sanman ◽

Melanie H. Cobb ◽

Lani F. Wu ◽

...

Keyword(s):

Intestinal Epithelial ◽

Epithelial Growth

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Insulin-like growth factor-binding protein-4 inhibits epithelial growth and proliferation in the rodent intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00349.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. G206-G219 ◽

Cited By ~ 2

Author(s):

Kaori Austin ◽

Derek Tsang ◽

Jennifer A. Chalmers ◽

Michael F. Maalouf ◽

Patricia L. Brubaker

Keyword(s):

Growth Factor ◽

Binding Protein ◽

Dependent Manner ◽

Insulin Like Growth Factor ◽

Intestinal Epithelial ◽

Ki 67 ◽

Factor Binding ◽

Gut Hormone ◽

And Control ◽

Epithelial Growth

Insulin-like growth factor-binding protein-4 (IGFBP-4) is a binding protein that modulates the action of insulin-like growth factor-1 (IGF-1), a growth factor whose presence is required for the intestinotrophic effects of glucagon-like peptide-2 (GLP-2). GLP-2 is a gut hormone that uses both IGF-1 and epidermal growth factor (EGF) as intermediary factors to promote intestinal growth. Therefore, to elucidate the mechanism through which IGFBP-4 regulates IGF-1 activity in the intestine, proliferation assays were conducted using rat intestinal epithelial cells (IEC-6). IGF-1 and EGF synergistically enhanced proliferation, an effect that was dose-dependently decreased by IGFBP-4 ( P < 0.05–0.001) in an IGF-1 receptor (R)- and MEK1/2- but not a phosphatidylinositol 3-kinase-dependent manner ( P > 0.05 for IGFBP-4 effects with IGF-1R and MEK1/2 inhibitors). Intestinal organoids derived from IGFBP-4 knockout mice demonstrated significantly greater Ki-67 expression and an enhanced surface area increase in response to IGF-1 treatment, compared with organoids from control mice ( P < 0.05–0.01). GLP-2 is also known to increase the mucosal expression of IGFBP-4 mRNA. To investigate whether this occurs through the actions of its intermediaries, IGF-1 and EGF, inducible intestinal epithelial-IGF-1R knockout and control mice were treated for 10 days with and without the pan-ErbB inhibitor, CI-1033. However, no differences in mucosal IGFBP-4 mRNA expression were found for any of the treatment groups ( P > 0.05). Consistently, IEC-6 cells treated with IGF-1 and/or EGF displayed no alteration in IGFBP-4 mRNA or in cellular and secreted IGFBP-4 protein ( P > 0.05). Overall, this study establishes that endogenous IGFBP-4 plays an important role in inhibiting IGF-1-induced intestinal epithelial proliferation and that mucosal IGFBP-4 expression is independent of IGF-1 and EGF. NEW & NOTEWORTHY This study demonstrates, for the first time, the inhibitory role of locally expressed insulin-like growth factor-binding protein-4 (IGFBP-4) on the intestinal proliferative actions of IGF-1 and supports the notion of the synergistic roles of IGF-1 and EGF in promoting intestinal epithelial growth. In turn, intestinal IGFBP-4 expression was not found to be regulated by IGF-1 and/or EGF.

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Mutational Landscape of the Proglucagon-Derived Peptides

Frontiers in Endocrinology ◽

10.3389/fendo.2021.698511 ◽

2021 ◽

Vol 12 ◽

Author(s):

Peter Lindquist ◽

Jakob S. Madsen ◽

Hans Bräuner-Osborne ◽

Mette M. Rosenkilde ◽

Alexander S. Hauser

Keyword(s):

Genetic Variation ◽

Amino Acid ◽

Therapeutic Potential ◽

Evolutionary Constraint ◽

Gene Products ◽

Missense Mutations ◽

Intestinal Epithelial ◽

Receptor Signalling ◽

The Impact ◽

Epithelial Growth

Strong efforts have been placed on understanding the physiological roles and therapeutic potential of the proglucagon peptide hormones including glucagon, GLP-1 and GLP-2. However, little is known about the extent and magnitude of variability in the amino acid composition of the proglucagon precursor and its mature peptides. Here, we identified 184 unique missense variants in the human proglucagon gene GCG obtained from exome and whole-genome sequencing of more than 450,000 individuals across diverse sub-populations. This provides an unprecedented source of population-wide genetic variation data on missense mutations and insights into the evolutionary constraint spectrum of proglucagon-derived peptides. We show that the stereotypical peptides glucagon, GLP-1 and GLP-2 display fewer evolutionary alterations and are more likely to be functionally affected by genetic variation compared to the rest of the gene products. Elucidating the spectrum of genetic variations and estimating the impact of how a peptide variant may influence human physiology and pathophysiology through changes in ligand binding and/or receptor signalling, are vital and serve as the first important step in understanding variability in glucose homeostasis, amino acid metabolism, intestinal epithelial growth, bone strength, appetite regulation, and other key physiological parameters controlled by these hormones.

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Membrane-bound vesicles associated with the microvilli in the midgut of the freshwater microcrustacean, Daphnia magna

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100076135 ◽

1983 ◽

Vol 41 ◽

pp. 480-481

Author(s):

Patricia L. Jansma

Keyword(s):

Daphnia Magna ◽

Intestinal Epithelial Cells ◽

Uranyl Acetate ◽

Intestinal Epithelial ◽

Chlamydomonas Reinhardii ◽

Thin Sections ◽

Saturated Water ◽

Cacodylate Buffer ◽

Membrane Bound ◽

Ethanol Series

The presence of the membrane bound vesicles or blebs on the intestinal epithelial cells has been demonstrated in a variety of vertebrates such as chicks, piglets, hamsters, and humans. The only invertebrates shown to have these microvillar blebs are two species of f1ies. While investigating the digestive processes of the freshwater microcrustacean, Daphnia magna, the presence of these microvillar blebs was noticed.Daphnia magna fed in a suspension of axenically grown green alga, Chlamydomonas reinhardii for one hour were narcotized with CO2 saturated water. The intestinal tracts were excised in 2% glutaraldehyde in 0.2 M cacodyl ate buffer and then placed in fresh 2% glutaraldehyde for one hour. After rinsing in 0.1 M cacodylate buffer, the sample was postfixed in 2% OsO4, dehydrated with a graded ethanol series, infiltrated and embedded with Epon-Araldite. Thin sections were stained with uranyl acetate and Reynolds lead citrate before viewing with the Philips EM 200.

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The protease phenotype and crystalline nature of the granules of intraepithelial mast cells in Trichinella spiralis-infected mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100140464 ◽

1995 ◽

Vol 53 ◽

pp. 818-819

Author(s):

D.S. Friend ◽

N. Ghildyal ◽

M.F. Gurish ◽

K.F. Austen ◽

R.L. Stevens

Keyword(s):

Small Intestine ◽

Mast Cells ◽

Epithelial Cells ◽

Lamina Propria ◽

Trichinella Spiralis ◽

Intestinal Epithelial ◽

Carboxypeptidase A ◽

C3h Mice ◽

Granule Morphology ◽

Crystalline Nature

Trichinella spiralis induces a profound mastocytosis and eosinophilia in the small intestine of the infected mouse. Mouse mast cells (MC) store in their granules various combinations of at least five chymotryptic chymases [designated mouse MC protease (mMCP) 1 to 5], two tryptic proteases designated mMCP-6 and mMCP-7 and an exopeptidase, carboxypeptidase A (mMC-CPA). Using antipeptide, protease -specific antibodies to these MC granule proteases, immunohistochemistry was done to determine the distribution, number and protease phenotype of the MCs in the small intestine and spleen 10 to >60 days after Trichinella infection of BALB/c and C3H mice. TEM was performed to evaluate the granule morphology of the MCs between intestinal epithelial cells and in the lamina propria (mucosal MCs) and in the submucosa, muscle and serosa of the intestine (submucosal MCs).As noted in the table below, the number of submucosal MCs remained constant throughout the study. In contrast, on day 14, the number of MCs in the mucosa increased ~25 fold. Increased numbers of MCs were observed between epithelial cells in the mucosal crypts, in the lamina propria and to a lesser extent, between epithelial cells of the intestinal villi.

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