Study of mucin turnover in the small intestine by in vivo labeling

Schneider, Hannah; Pelaseyed, Thaher; Svensson, Frida; Johansson, Malin

doi:10.1038/s41598-018-24148-x

Cited by 73 publications

(60 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even during extreme zinc deficiency, the fecal excretion of zinc can be observed, which is defined as the “obligatory fecal loss” [ 2 ]. The intestinal epithelium and the overlying mucus layer undergo cycles of renewal [ 49 , 50 ] resulting in a complete turnover of the mucins, which is said to occur much faster than that of the underlying mucosa [ 51 ]. Considering the amount of zinc bound to mucins, the fast renewal of the intestinal mucus layer might play an important role in the fecal zinc loss as the mucins are possibly excreted together with a remainder of tightly bound zinc.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins

Maares

Keil

Koza

et al. 2018

IJMS

View full text Add to dashboard Cite

The investigation of luminal factors influencing zinc availability and accessibility in the intestine is of great interest when analyzing parameters regulating intestinal zinc resorption. Of note, intestinal mucins were suggested to play a beneficial role in the luminal availability of zinc. Their exact zinc binding properties, however, remain unknown and the impact of these glycoproteins on human intestinal zinc resorption has not been investigated in detail. Thus, the aim of this study is to elucidate the impact of intestinal mucins on luminal uptake of zinc into enterocytes and its transfer into the blood. In the present study, in vitro zinc binding properties of mucins were analyzed using commercially available porcine mucins and secreted mucins of the goblet cell line HT-29-MTX. The molecular zinc binding capacity and average zinc binding affinity of these glycoproteins demonstrates that mucins contain multiple zinc-binding sites with biologically relevant affinity within one mucin molecule. Zinc uptake into the enterocyte cell line Caco-2 was impaired by zinc-depleted mucins. Yet this does not represent their form in the intestinal lumen in vivo under zinc adequate conditions. In fact, zinc-uptake studies into enterocytes in the presence of mucins with differing degree of zinc saturation revealed zinc buffering by these glycoproteins, indicating that mucin-bound zinc is still available for the cells. Finally, the impact of mucins on zinc resorption using three-dimensional cultures was studied comparing the zinc transfer of a Caco-2/HT-29-MTX co-culture and conventional Caco-2 monoculture. Here, the mucin secreting co-cultures yielded higher fractional zinc resorption and elevated zinc transport rates, suggesting that intestinal mucins facilitate the zinc uptake into enterocytes and act as a zinc delivery system for the intestinal epithelium.

show abstract

Section: Discussionmentioning

confidence: 99%

In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins

Maares

Keil

Koza

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…Mucoadhesive polymers can prolong the residence time of the carriers at the site of absorption . Since the intestinal mucus turnover time ranges between 30 min and few hours, it can be considered slower than the time needed for absorption . Chitosan, a mucoadhesive polymer, has been used as coating or carrier for micro‐ and nanoparticles for delivery of proteins improving their oral bioavailability .…”

Section: Introductionmentioning

confidence: 99%

Polymeric Lids for Microcontainers for Oral Protein Delivery

Mazzoni

Jacobsen

Mortensen

et al. 2019

Macromolecular Bioscience

View full text Add to dashboard Cite

Oral delivery of proteins and peptides is one of the main challenges in pharmaceutical drug development. Microdevices have the possibility to protect the therapeutics until release is desired, avoiding losses by degradation. One type of microdevice is polymeric microcontainers. In this study, lysozyme is chosen as model protein and loaded into microcontainers with the permeation enhancer sodium decanoate (C10). The loaded microcontainers are sealed and functionalized by applying polymeric lids onto the cavity of the devices. The first lid is poly(lactic-co-glycolic) acid (PLGA) and on top of this either polyethylene glycol (PEG) or chitosan is applied (PLGA+PEG or PLGA+chitosan, respectively). The functionalization is evaluated in vitro for morphology, drug release, and mucoadhesive properties. These are coupled with in vitro and ex vivo studies using Caco-2 cells, Caco-2/HT29-MTX-E12 co-cultures, and porcine intestinal tissue. PLGA+chitosan shows slower release compared to PLGA+PEG or only PLGA in buffer and the transport of lysozyme across cell cultures is not enhanced compared to the bulk powder. Microcontainers coated with chitosan or PEG demonstrate a three times stronger adhesion during ex vivo mucoadhesion studies compared to samples without coatings. Altogether, functionalized microcontainers with mucoadhesive properties and tunable release for oral protein delivery are developed and characterized.

show abstract

“…Copper-catalyzed azide-alkyne additions have been used but are traditionally thought to be cytotoxic to living cells and tissues (Baskin et al, 2007). Copper-free azide-alkyne cycloadditions (CFAACs) have gained some prominence due to their biocompatibility and have been used to label intestinal goblet cells in fixed tissue (Schneider, Pelaseyed, Svensson, & Johansson, 2018). CFAACs have not previously been used ex vivo to label goblet cells in cellularly heterogenous tissues.…”

Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal peptide regulates ileal goblet cell production in mice

Schwerdtfeger

Tobet

2020

Physiol Rep

View full text Add to dashboard Cite

Innervation of the intestinal mucosa has gained more attention with demonstrations of tuft and enteroendocrine cell innervation. However, the role(s) these fibers play in maintaining the epithelial and mucus barriers are still poorly understood. This study therefore examines the proximity of mouse ileal goblet cells to neuronal fibers, and the regulation of goblet cell production by vasoactive intestinal peptide (VIP). An organotypic intestinal slice model that maintains the cellular diversity of the intestinal wall ex vivo was used. An ex vivo copper‐free click‐reaction to label glycosaminoglycans was used to identify goblet cells. Pharmacological treatment of slices was used to assess the influence of VIP receptor antagonism on goblet cell production and neuronal fiber proximity. Goblet cells were counted and shown to have at least one peripherin immunoreactive fiber within 3 µm of the cell, 51% of the time. Treatment with a VIP receptor type I and II antagonist (VPACa) resulted in an increase in the percentage of goblet cells with peripherin fibers. Pharmacological treatments altered goblet cell counts in intestinal crypts and villi, with tetrodotoxin and VPACa substantially decreasing goblet cell counts. When cultured with 5‐Ethynyl‐2’‐deoxyuridine (EdU) as an indicator of cell proliferation, colocalization of labeled goblet cells and EdU in ileal crypts was decreased by 77% when treated with VPACa. This study demonstrates a close relationship of intestinal goblet cells to neuronal fibers. By using organotypic slices from mouse ileum, vasoactive intestinal peptide receptor regulation of gut wall goblet cell production was revealed.

show abstract

Study of mucin turnover in the small intestine by in vivo labeling

Cited by 73 publications

References 27 publications

In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins

In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins

Polymeric Lids for Microcontainers for Oral Protein Delivery

Vasoactive intestinal peptide regulates ileal goblet cell production in mice

Contact Info

Product

Resources

About