Up-regulation of syndecan-2 in proximal colon correlates with acute inflammation

FASEB J. 2019 Oct;33(10):11381-11395. doi: 10.1096/fj.201900561R. Epub 2019 Jul 16.

Abstract

We previously reported that syndecan-2 expression is increased on the colonic epithelium during chronic inflammation. Here, we report that syndecan-2 exhibits a different pattern of site-specific colonic expression during acute inflammation. Syndecan-2 expression was up-regulated predominantly in the proximal colon of dextran sulfate sodium-induced colitis mice. The colitis-associated up-regulation of syndecan-2 was barely detected in Rag-1-/- (recombination activating gene 1 knockout) mice under colitis-inducing conditions. Increased syndecan-2 expression correlated with increased levels of infiltrated CD4+ IL-17A+ T cells in the proximal colon. Serum levels of IL-17A were increased during the acute inflammatory response in normal mice but not Rag-1-/- mice. IL-17A directly induced IL-17 receptor (IL-17RA) and syndecan-2 expression in ex vivo-cultured proximal colon tissues and adenoma cell lines from proximal colon. IL-17RA knockdown reduced the IL-17A-mediated syndecan-2 expression in SNU1235 cells. No elevation of syndecan-2 or IL-17RA was observed in colonic tissues from IL-17A-/- mice during colitis induction. Finally, increased expression of syndecan-2 and IL-17RA was observed in the proximal colons of cecal ligation and puncture-induced sepsis mice and infectious pan colitis patients. Together, these data suggest that acute inflammation induces syndecan-2 expression predominantly in the proximal colon via IL-17A-IL-17RA signaling during the early stage of the inflammatory response and that proximal colonic syndecan-2 might be a biomarker for acute inflammation.-Hong, H., Song, H.-K., Hwang, E. S., Lee, A. R., Han, D. S., Kim, S.-E., Oh, E.-S. Up-regulation of syndecan-2 in proximal colon correlates with acute inflammation.

Keywords: IL17RA; colitis; proteoglycan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colon / drug effects
  • Colon / metabolism*
  • Dextran Sulfate / pharmacology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Interleukin-17 / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Interleukin-17 / metabolism
  • Signal Transduction / physiology
  • Syndecan-2 / metabolism*
  • Transcriptional Activation / physiology
  • Up-Regulation / physiology*

Substances

  • Interleukin-17
  • Receptors, Interleukin-17
  • SDC2 protein, human
  • Syndecan-2
  • Dextran Sulfate