Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice
Frontiers in Cell and Developmental Biology, ISSN: 2296-634X, Vol: 9, Page: 632805
2021
- 10Citations
- 12Captures
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Metrics Details
- Citations10
- Citation Indexes10
- 10
- Captures12
- Readers12
- 12
Article Description
Aldo-keto reductase 1B10 (AKR1B10) is downregulated in human ulcerative colitis (UC) and colorectal cancer, being a potential pathogenic factor of these diseases. Aldo-keto reductase 1B8 (AKR1B8) is the ortholog in mice of human AKR1B10. Targeted AKR1B8 deficiency disrupts homeostasis of epithelial self-renewal and leads to susceptibility to colitis and carcinogenesis. In this study, we found that in AKR1B8 deficient mice, Muc2 expression in colon was diminished, and permeability of colonic epithelium increased. Within 24 h, orally administered FITC-dextran penetrated into mesenteric lymph nodes (MLN) and liver in AKR1B8 deficient mice, but not in wild type controls. In the colon of AKR1B8 deficient mice, neutrophils and mast cells were markedly infiltrated, γδT cells were numerically and functionally impaired, and dendritic cell development was altered. Furthermore, Th1, Th2, and Th17 cells decreased, but Treg and CD8T cells increased in the colon and MLN of AKR1B8 deficient mice. In colonic epithelial cells of AKR1B8 deficient mice, p-AKT (T308 and S473), p-ERK1/2, p-IKBα, p-p65 (S536), and IKKα expression decreased, accompanied with downregulation of IL18 and CCL20 and upregulation of IL1β and CCL8. These data suggest AKR1B8 deficiency leads to abnormalities of intestinal epithelial barrier and immunity in colon.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85101880103&origin=inward; http://dx.doi.org/10.3389/fcell.2021.632805; http://www.ncbi.nlm.nih.gov/pubmed/33644071; https://www.frontiersin.org/articles/10.3389/fcell.2021.632805/supplementary-material/10.3389/fcell.2021.632805.s001; http://dx.doi.org/10.3389/fcell.2021.632805.s001; https://www.frontiersin.org/articles/10.3389/fcell.2021.632805/full; https://dx.doi.org/10.3389/fcell.2021.632805; https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.632805/full; https://dx.doi.org/10.3389/fcell.2021.632805.s001
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