Alginate oligosaccharides enhance small intestine cell integrity and migration ability

Life Sci. 2020 Oct 1:258:118085. doi: 10.1016/j.lfs.2020.118085. Epub 2020 Jul 12.

Abstract

Background: An integral intestinal barrier is essential for intestinal homeostasis. Yet, as a side effect of cancer treatment, chemotherapeutic drugs have been reported to cause mucositis. In a recent study, we found that alginate oligosaccharides (AOS) prevent busulfan induced intestinal mucositis. However, it is not known if AOS improves small intestine epithelial cell integrity and migration, which are two essential processes for maintaining the mechanical barrier function of the small intestine. In the current investigation, we aimed to explore the effects of AOS on the integrity and migration of small intestine cells using swine intestinal epithelial IPEC-J2 cells.

Methods: Cell integrity was determined using the TEER assay. Cell migration capability was detected using a wound healing experiment. Small interfering RNA (siRNA) was used to inhibit mannose receptor (MR) expression. Western blotting and immunofluorescence staining were used to determine protein expression.

Results: Increasing levels of AOS improved cell integrity as measure by TEER. At the same time, AOS improved IPEC-J2 cell migration capacity as shown in the wound closure assay. It is interesting to note that AOS increased the expression of intestinal microvillus proteins and junction proteins to benefit cell integrity. MR siRNA blocked the action of AOS on cell integrity and cell migration and inhibited the expression of microvillus and cell junction proteins.

Conclusion: We identified the underlying mechanisms by which AOS improved small intestinal mucositis. As a novel, natural food additive, AOS may be administered to prevent intestinal mucositis induced by chemotherapy or other issues.

Keywords: Alginate oligosaccharides (AOS); Integrity; Junction proteins; Mannose receptor (MR).

MeSH terms

  • Alginates / pharmacology*
  • Animals
  • Cell Line
  • Cell Movement / drug effects*
  • Intestine, Small / cytology*
  • Lectins, C-Type / metabolism
  • Mannose Receptor
  • Mannose-Binding Lectins / metabolism
  • Microfilament Proteins / metabolism
  • Microvilli / drug effects
  • Microvilli / metabolism
  • Myosins / metabolism
  • Oligosaccharides / pharmacology*
  • RNA, Small Interfering / metabolism
  • Receptors, Cell Surface / metabolism
  • Swine
  • Tight Junction Proteins / metabolism
  • Wound Healing / drug effects

Substances

  • Alginates
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Microfilament Proteins
  • Oligosaccharides
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Tight Junction Proteins
  • villin
  • Myosins