Dataset Information

Dietary Red Raspberry Reduces Colorectal Inflammation and Carcinogenic Risk in Mice with Dextran Sulfate Sodium-Induced Colitis.

ABSTRACT: BACKGROUND:Ulcerative colitis causes recurring intestinal mucosal injury and sustained inflammation, increasing the likelihood of colorectal cancer (CRC) development. Dietary red raspberry (RB) is a rich source of phytonutrients known to have anti-inflammatory activity; however, the role of RB on CRC prevention in chronic colitis has not been examined. OBJECTIVE:This study examined the effects of dietary RB supplementation on inflammation, epithelium repair, and oncogenic signaling in dextran sulfate sodium (DSS)-induced chronic colitis in mice. METHODS:Six-week-old male C57BL/6J mice were fed a control or RB (5% of dry feed weight; n = 12/group) diet for 10 wk. Starting from the fourth week, mice were administered 2 repeated cycles of 1% DSS (7-d DSS treatment plus 14-d recovery) and were monitored daily for disease activity index (DAI) score. Colonic tissues were collected at the end of the study for histochemical, immunohistochemical, and biochemical analysis of inflammation, differentiation and proliferation markers. RESULTS:RB supplementation reduced the DAI score and histologic damage (by 38.9%; P ? 0.01), expression of inflammatory mediators (by 20-70%; P ? 0.01), infiltration of CD4 T cells (by 50%; P ? 0.05), and ?4?7 integrin and related adhesion molecules (by 33.3%; P ? 0.01). Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ? 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ? 0.01), ?-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ? 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%). CONCLUSION:RB supplementation reduced DAI score and the risk of CRC development during recurring colitis in mice, suggesting that RB is a possible dietary supplement for patients with ulcerative colitis and related gut inflammatory diseases.

SUBMITTER: Bibi S

PROVIDER: S-EPMC7263837 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Dietary Red Raspberry Reduces Colorectal Inflammation and Carcinogenic Risk in Mice with Dextran Sulfate Sodium-Induced Colitis.

Bibi Shima S Du Min M Zhu Mei-Jun MJ

The Journal of nutrition 20180501 5

<h4>Background</h4>Ulcerative colitis causes recurring intestinal mucosal injury and sustained inflammation, increasing the likelihood of colorectal cancer (CRC) development. Dietary red raspberry (RB) is a rich source of phytonutrients known to have anti-inflammatory activity; however, the role of RB on CRC prevention in chronic colitis has not been examined.<h4>Objective</h4>This study examined the effects of dietary RB supplementation on inflammation, epithelium repair, and oncogenic signalin ...[more]

PMID: 29897487

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Project description:Background & aimsFibrosis development in ulcerative colitis is associated directly with the severity of mucosal inflammation, which increases the risk of colorectal cancer. The transforming growth factor-β (TGF-β) signaling pathway is an important source of tissue fibrogenesis, which is stimulated directly by reactive oxygen species produced from nicotinamide adenine dinucleotide phosphate oxidases (NOX). Among members of the NOX family, NOX4 expression is up-regulated in patients with fibrostenotic Crohn's disease (CD) and in dextran sulfate sodium (DSS)-induced murine colitis. The aim of this study was to determine whether NOX4 plays a role in fibrogenesis during inflammation in the colon using a mouse model.MethodsAcute and recovery models of colonic inflammation were performed by DSS administration to newly generated Nox4-/- mice. Pathologic analysis of colon tissues was performed, including detection of immune cells, proliferation, and fibrotic and inflammatory markers. RNA sequencing was performed to detect differentially expressed genes between Nox4-/- and wild-type mice in both the untreated and DSS-treated conditions, followed by functional enrichment analysis to explore the molecular mechanisms contributing to pathologic differences during DSS-induced colitis and after recovery.ResultsNox4-/- mice showed increased endogenous TGF-β signaling in the colon, increased reactive oxygen species levels, intensive inflammation, and an increased fibrotic region after DSS treatment compared with wild-type mice. Bulk RNA sequencing confirmed involvement of canonical TGF-β signaling in fibrogenesis of the DSS-induced colitis model. Up-regulation of TGF-β signaling affects collagen activation and T-cell lineage commitment, increasing the susceptibility for inflammation.ConclusionsNox4 protects against injury and plays a crucial role in fibrogenesis in DSS-induced colitis through canonical TGF-β signaling regulation, highlighting a new treatment target.

Project description:Alterations in the intestinal lymphatic network are pathological processes as related to inflammatory bowel disease (IBD). In this study, we demonstrated that reduction in inflammation-induced lymphangiogenesis ameliorates experimental acute colitis. A soluble and stable angiopoietin-1 (Ang1) variant, COMP-Ang1, possesses anti-inflammatory and angiogenic effects. We investigated the effects of COMP-Ang1 on an experimental colonic inflammation model. Experimental colitis was induced in mice by administering 3% dextran sulfate sodium (DSS) via drinking water. We determined body weight, disease activity indices, histopathological scores, lymphatic density, anti-ER-HR3 staining, and the expression of members of the vascular endothelial growth factor (VEGF) family and various inflammatory cytokines in the mice. The density of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and VEGFR-3-positive lymphatic vessels increased in mice with DSS-induced colitis. We observed that COMP-Ang1-treated mice showed less weight loss, fewer clinical signs of colitis, and longer colons than Ade-DSS-treated mice. COMP-Ang1 also significantly reduced the density of LYVE-1-positive lymphatic vessels and the disruption of colonic architecture that is normally associated with colitis and repressed the immunoregulatory response. Further, COMP-Ang1 treatment reduced both M1 and M2 macrophage infiltration into the inflamed colon, which involved inhibition of VEGF-C and D expression. Thus, COMP-Ang1, which acts by reducing inflammation-induced lymphangiogenesis, may be used as a novel therapeutic for the treatment of IBD and other inflammatory diseases.Key messagesCOMP-Ang1 decreases inflammatory-induced lymphangiogenesis in experimental acute colitis. COMP-Ang1 improves the symptom of DSS-induced inflammatory response. COMP-Ang1 reduces the expression of pro-inflammatory cytokines in inflamed colon. COMP-Ang1 reduces the expression of VEGFs in inflamed colon. COMP-Ang1 prevents infiltration of macrophages in a DSS-induced colitis model.

Dataset Information

Dietary Red Raspberry Reduces Colorectal Inflammation and Carcinogenic Risk in Mice with Dextran Sulfate Sodium-Induced Colitis.

Publications

Dietary Red Raspberry Reduces Colorectal Inflammation and Carcinogenic Risk in Mice with Dextran Sulfate Sodium-Induced Colitis.

Similar Datasets

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