Original Research ARTICLE
Dipotassium Glycyrrhizate improves intestinal mucosal healing by modulating extracellular matrix remodeling genes and restoring epithelial barrier functions
- 1Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Italy
Gut mucosal healing (MH) is considered a key therapeutic target and prognostic parameter in the management of inflammatory bowel disease (IBD). The dipotassium glycyrrhizate (DPG), a salt of the glycoconjugated triterpene glycyrrhizin, has been shown to inhibit the High Mobility Group Box 1 (HMGB1) protein, an allarmin strongly implicated in the pathogenesis of most inflammatory and auto-immune disorders. Here we discuss new insights on how DPG acts on MH comparing the acute phase and the recovery phase from experimental colitis in mice. We found that DPG strongly accelerates MH by differently regulating pro-inflammatory (CXCL1, CXCL3, CXCL5, PTGS2, IL-1β, IL-6, CCL12, CCL7) and wound healing (COL3A1, MMP9, VTN, PLAUR, SERPINE, CSF3, FGF2, FGF7, PLAT, TIMP1) genes as observed only during the recovery phase of colitis. Relevant issue is the identification of extracellular matrix (ECM) remodeling genes, VTN and PLAUR, as crucial genes to achieve MH during DPG treatment. Furthermore, a noticeable recovery of intestinal epithelial barrier structural organization, wound repair ability and functionality is observed in two human colorectal adenocarcinoma cell lines exposed to DPG during inflammation. Thus, our study identifies DPG as a potent tool for controlling intestinal inflammation and improving MH.
Keywords: Dipotassium glycyrrhizate, mucosal healing, DSS-induced colitis, Plaur, VTN
Received: 11 Dec 2018;
Accepted: 11 Apr 2019.
Edited by:Andrew M. Smith, University College London, United Kingdom
Reviewed by:Marco E. Bianchi, Vita-Salute San Raffaele University, Italy
Pallavi Garg, Georgia State University, United States
Copyright: © 2019 Vitali. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Roberta Vitali, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Rome, Italy, email@example.com