Serum Amyloid A1 Is an Epithelial Prorestitutive Factor

Am J Pathol. 2018 Apr;188(4):937-949. doi: 10.1016/j.ajpath.2017.12.013. Epub 2018 Jan 31.

Abstract

Several proteins endogenously produced during the process of intestinal wound healing have demonstrated prorestitutive properties. The presence of serum amyloid A1 (SAA1), an acute-phase reactant, within inflamed tissues, where it exerts chemotaxis of phagocytes, is well recognized; however, a putative role in intestinal wound repair has not been described. Herein, we show that SAA1 induces intestinal epithelial cell migration, spreading, and attachment through a formyl peptide receptor 2-dependent mechanism. Induction of the prorestitutive phenotype is concentration and time dependent and is associated with epithelial reactive oxygen species production and alterations in p130 Crk-associated substrate staining. In addition, using a murine model of wound recovery, we provide evidence that SAA1 is dynamically and temporally regulated, and that the elaboration of SAA1 within the wound microenvironment correlates with the influx of SAA1/CD11b coexpressing immune cells and increases in cytokines known to induce SAA expression. Overall, the present work demonstrates an important role for SAA in epithelial wound recovery and provides evidence for a physiological role in the wound environment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cell Adhesion
  • Cell Movement
  • Crk-Associated Substrate Protein / metabolism
  • Cytokines / metabolism
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Mice, Inbred C57BL
  • Reactive Oxygen Species / metabolism
  • Receptors, Formyl Peptide / metabolism
  • Serum Amyloid A Protein / metabolism*
  • Signal Transduction
  • Wound Healing

Substances

  • Crk-Associated Substrate Protein
  • Cytokines
  • Reactive Oxygen Species
  • Receptors, Formyl Peptide
  • Saa2 protein, mouse
  • Serum Amyloid A Protein
  • formyl peptide receptor 2, mouse