Dipotassium Glycyrrhizate Improves Intestinal Mucosal Healing by Modulating Extracellular Matrix Remodeling Genes and Restoring Epithelial Barrier Functions

TitleDipotassium Glycyrrhizate Improves Intestinal Mucosal Healing by Modulating Extracellular Matrix Remodeling Genes and Restoring Epithelial Barrier Functions
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2019
AuthorsStronati, L., Palone Francesca, Negroni Anna, Colantoni Eleonora, Mancuso Anna Barbara, Cucchiara Salvatore, Cesi Vincenzo, Isoldi Sara, and Vitali Roberta
JournalFrontiers in Immunology
Volume10
Date PublishedFeb-04-2021
ISSN16643224
Keywordsanimal, animal experiment, animal model, animal tissue, Animals, article, C57BL mouse, Caco-2 cell line, Caco-2 Cells, cell adhesion, Cell Line, colitis, collagen type 3, controlled study, CXCL1 chemokine, CXCL3 chemokine, cytokine, Cytokines, dipotassium glycyrrhizate, down regulation, drug effect, Electric resistance, Epithelial Cells, epithelial derived neutrophil activating factor 78, epithelium cell, extracellular matrix, feces analysis, Female, Fibroblast Growth Factor 2, gelatinase B, Gene expression, glycyrrhizic acid, granulocyte colony stimulating factor, high mobility group B1 protein, histology, HMGB1 Protein, HT-29 cell line, HT29 Cells, human, human cell, Humans, Immunoblotting, Immunofluorescence, Inbred C57BL, inflammation, inflammatory bowel disease, interleukin 1beta, interleukin 6, Intestinal Mucosa, intestine mucosa, keratinocyte growth factor, metabolism, Mice, monocyte chemotactic protein 3, monocyte chemotactic protein 5, mouse, mRNA expression level, mucosa inflammation, nonhuman, pathogenesis, plasminogen activator, prostaglandin synthase, rat, real time polymerase chain reaction, reserpine, RNA isolation, signal transduction, stress fiber, tight junction, tissue inhibitor of metalloproteinase 1, Tumor, tumor cell line, unclassified drug, upregulation, urokinase receptor, vitronectin, wound healing, wound healing assay
Abstract

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. Copyright © 2019 Stronati, Palone, Negroni, Colantoni, Mancuso, Cucchiara, Cesi, Isoldi and Vitali.

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URLhttps://www.frontiersin.org/article/10.3389/fimmu.2019.00939
DOI10.3389/fimmu.2019.0093910.3389/fimmu.2019.00939.s00110.3389/fimmu.2019.00939.s002
Short TitleFront. Immunol.