Naturally Occurring N-Terminal Fragments of Bovine Milk Osteopontin Are Transported across Models of the Intestinal Barrier

Author:

Christensen Brian1ORCID,Nielsen Nanna R.1,Sørensen Marie R.1,Jacobsen Lotte N.2,Ostenfeld Marie S.2,Sørensen Esben S.1ORCID

Affiliation:

1. Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark

2. Arla Foods Ingredients Group P/S, DK-8260 Viby J, Denmark

Abstract

Osteopontin (OPN) is a bioactive integrin-binding protein found in high concentrations in milk, where it is present both as a full-length protein and as several N-terminally derived fragments. OPN resists gastric digestion, and via interaction with receptors in the gut or by crossing the intestinal barrier into circulation, ingested milk OPN may influence physiological processes. The aim of this study was to investigate OPN interaction with intestinal cells and its transport across models of the intestinal barrier. Immunodetection of OPN incubated with Caco-2 cells at 4 °C and 37 °C showed that OPN binds to the intestinal cells, but it is not internalised. Transepithelial transport was studied using mono- and co-cultures of Caco-2 cells and mucus-producing HT29-MTX cells in transwell membranes. OPN was shown to cross the barrier models in a time-, temperature-, and energy-dependent process inhibited by wortmannin, indicating that the transport takes place via the transcytosis pathway. Analyses of the naturally occurring milk mixture of full-length and N-terminal fragments showed that the N-terminal fragments of OPN bound intestinal cells most effectively and that the fragments were transported across the intestinal membrane models. This suggests that proteolytic processing of OPN increases its biological activity after ingestion.

Funder

Danish Levy Foundation

Arla Foods Ingredients Group P/S, Denmark

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Synergistic effect of lactoferrin and osteopontin on intestinal barrier injury;International Journal of Biological Macromolecules;2023-12

2. Pathomechanisms of Diabetic Kidney Disease;Journal of Clinical Medicine;2023-11-27

3. Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response;Cancers;2023-07-03

4. Milk Osteopontin and Human Health;Nutrients;2023-05-23

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