Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6

Cells. 2019 Sep 12;8(9):1074. doi: 10.3390/cells8091074.


Hyaluronan (HA) has proven to be beneficial in the treatment of several diseases. Recently, it has been shown that the local application of HA (IBD98E) improves endoscopic and clinical outcomes in subjects with active distal ulcerative colitis (UC). However, the mechanisms by which this polysaccharide exerts its beneficial effects are unclear. Here, we demonstrated that HA treatment in vitro and in vivo improved mucosal healing by accelerating intestinal epithelial regeneration. Indeed, mice treated with HA showed a faster recovery from colitis and reduced endoscopic signs of mucosal inflammation compared to those receiving saline. Furthermore, histological analysis revealed less ulcerated mucosa in mice treated with HA, characterized by re-epithelialized areas. TSG-6, the secreted product of TNF-stimulated gene-6, is an HA-binding protein shown previously to have tissue-protective properties and promote wound healing. Mucosal levels of TSG-6 increased in UC patients compared to the healthy controls and also after wounding in mice. TSG-6 deletion prevented the beneficial properties of HA in mucosal wound repair, suggesting that the interaction of HA with TSG-6 is crucial for intestinal epithelial regeneration. Overall these results are consistent with HA having a therapeutic effect via the promotion of mucosal healing in patients with ulcerative colitis.

Keywords: TSG-6; epithelial regeneration; experimental colitis; hyaluronan; inflammatory bowel disease; mucosal healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Caco-2 Cells
  • Cell Adhesion Molecules / metabolism*
  • Colitis, Ulcerative / drug therapy*
  • Female
  • Humans
  • Hyaluronic Acid / pharmacology*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Middle Aged


  • Cell Adhesion Molecules
  • TNFAIP6 protein, human
  • Tnfaip6 protein, mouse
  • Hyaluronic Acid