Peroxisome proliferator-activated receptor-γ is downregulated in ulcerative colitis and is involved in experimental colitis-associated neoplasia

Dou, Xiaotan; Xiao, Junhua; Jin, Ziliang; Zheng, Ping

doi:10.3892/ol.2015.3397

Cited by 32 publications

(20 citation statements)

References 33 publications

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“…Similarly, no difference in PPAR γ expression was noted for IBD, although there was slight increased expression in CD and slightly reduced expression for UC, compared to Normal. This data is congruent with previous reports showing downregulation of PPAR γ expression in UC and unchanged expression from normal in CD [ 39 , 40 ]. PPAR γ was significantly increased for both C-IBS and D-IBS.…”

Section: Discussionsupporting

confidence: 93%

β-Catenin Regulation in Sporadic Colorectal Carcinogenesis: Not as Simple as APC

Fredericks

Dealtry

Roux

2018

Canadian Journal of Gastroenterology and Hepatology

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Background The wnt/APC/β-catenin pathway is a critical initiator in colorectal carcinogenesis in both hereditary and sporadic colorectal cancer (CRC). The progression of this process remains incompletely understood, although inflammation is pivotal. Drivers of inflammation are elevated in malignant tissue and have been shown to regulate β-catenin expression. Interleukin-17A (IL-17A) is protumorigenic at elevated levels via COX-2 stimulation. Elevated peroxisome proliferator-activated receptor γ (PPARγ) expression has reduced risk of carcinogenesis and good overall prognosis in established CRC. Activation of PPARγ has inhibitory effect on β-catenin. Methods Using qPCR and IHC, we compared β-catenin, PPARγ, COX-2, and IL-17A in the colonic mucosa of patients with sporadic CRC, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS), against a normal control population. Results β-catenin mRNA and protein expression progressively increased from the Normal group, through IBS and IBD reaching statistical significance in CRC. COX-2 mRNA levels increased similarly with statistical significance in IBD and CRC. However, COX-2 protein expression was inverted with significant expression in the Normal and IBS groups and reduced levels in IBD and CRC. PPARγ mRNA expression was unchanged in IBD and CRC but was significantly elevated in the IBS. IL-17A mRNA was significantly reduced in IBS and CRC but unchanged in IBD. There were no differences in all parameters tested in the Normal and IBS groups. Conclusion β-catenin is confirmed as a major driver of colorectal carcinogenesis but is controlled by many more players other than APC. Elevated levels of PPARγ may have an anticarcinogenic effect. The role of COX-2 expression, especially its posttranscriptional regulation in colorectal cancer, needs further elucidation.

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Section: Discussionsupporting

confidence: 93%

β-Catenin Regulation in Sporadic Colorectal Carcinogenesis: Not as Simple as APC

Fredericks

Dealtry

Roux

2018

Canadian Journal of Gastroenterology and Hepatology

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“…Previously, the expression of PPAR-γ has been reported as reduced in active UC and comparable with normal colon in active CD. 10 Taken altogether, our results suggest that MUC2 expression is independent of NLRP6 activity, however, there is insufficient evidence to suggest the negative regulation of NLRP6 by PPAR-γ .…”

mentioning

confidence: 52%

Nod-Like Receptor Pyrin-Containing Protein 6 (NLRP6) Is Up-regulated in Ileal Crohn’s Disease and Differentially Expressed in Goblet Cells

Ranson

Veldhuis

Mitchell

et al. 2018

Cellular and Molecular Gastroenterology and Hepatology

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“…PPARγ was reported to inhibit the production of inflammatory cytokines in different cell types by interfering with TLR4-dependent signaling pathway [ 76 ]. A clinical study comparing a healthy control group with Crohn’s disease patients found that the expression of PPARγ in the intestinal tissue of patients with ulcerative colitis (UC) was significantly decreased [ 77 ]. Moreover, it has been shown that prebiotics such as oligosaccharides can reduce proinflammatory cytokines in intestinal Caco-2 cells, and that this reduction is dependent upon the activation of PPARγ [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Prebiotic Blend Product Prevents Irritable Bowel Syndrome in Mice by Improving Gut Microbiota and Modulating Immune Response

et al. 2017

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Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder yet it still lacks effective prevention therapies. The aim of this study is to determine whether a novel prebiotic blend (PB) composed of fructo-oligosaccharide (FOS), galactooligosaccharide (GOS), inulin and anthocyanins could be effective in preventing the development of IBS. We explored the possible mechanisms both in animal and in cells. Post-infectious IBS models in C57BL/6 mice were established and were pretreated with the PB, PB and probiotic strains 8 weeks in advance of infection. Eight weeks after infection, intestinal tissues were collected for assessing histomorphology, visceral sensitivity, barrier function, pro-inflammatory cytokines expression and proteomics analysis. Fecal samples were also collected for microbiota analysis. The pro-inflammatory cytokines expression in Caco-2 cells were evaluated after co-incubation with PB and Salmonella typhimurium 14028. The results showed that PB significantly decreased the pro-inflammatory cytokines both in infected Caco-2 cells and PI-IBS models. The loss of body weight, decreased expression of tight junction protein Occludin (OCLN), and changes of the microbiota composition induced by infections could be greatly improved by PB intervention (p < 0.05). The proteomics analysis revealed that this function was associated with Peroxisome proliferator-activated receptor (PPAR)γ pathway.

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Peroxisome proliferator-activated receptor-γ is downregulated in ulcerative colitis and is involved in experimental colitis-associated neoplasia

Cited by 32 publications

References 33 publications

β-Catenin Regulation in Sporadic Colorectal Carcinogenesis: Not as Simple as APC

β-Catenin Regulation in Sporadic Colorectal Carcinogenesis: Not as Simple as APC

Nod-Like Receptor Pyrin-Containing Protein 6 (NLRP6) Is Up-regulated in Ileal Crohn’s Disease and Differentially Expressed in Goblet Cells

A Novel Prebiotic Blend Product Prevents Irritable Bowel Syndrome in Mice by Improving Gut Microbiota and Modulating Immune Response

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