Functional analysis of isoflavones using patient-derived human colonic organoids
Autor: | Minami Hama, Sho Anzai, Junichi Takahashi, Hady Yuki Sugihara, Shigeru Oshima, Tomohiro Mizutani, M. Tsuchiya, Hiromichi Shimizu, Sayaka Nagata, Go Ito, Mamoru Watanabe, Yui Hiraguri, Kiichiro Tsuchiya, Sayaka Takeoka, Ryuichi Okamoto, Shiro Yui, Reiko Kuno, Ami Kawamoto, Kohei Suzuki |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Biophysics Genistein Biochemistry Inflammatory bowel disease Receptor tyrosine kinase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Intestinal mucosa Medicine Progenitor cell Molecular Biology biology business.industry Daidzein Cell Biology Isoflavones medicine.disease 030104 developmental biology chemistry Hepatocyte Growth Factor Receptor 030220 oncology & carcinogenesis Cancer research biology.protein business |
Zdroj: | Biochemical and Biophysical Research Communications. 542:40-47 |
ISSN: | 0006-291X |
Popis: | Inflammatory bowel disease (IBD) comprises two major subtypes, ulcerative colitis (UC) and Crohn's disease, which are multifactorial diseases that may develop due to genetic susceptibility, dysbiosis, or environmental factors. Environmental triggers of IBD include food-borne factors, and a previous nationwide survey in Japan identified pre-illness consumption of isoflavones as a risk factor for UC. However, the precise mechanisms involved in the detrimental effects of isoflavones on the intestinal mucosa remain unclear. The present study employed human colonic organoids (hCOs) to investigate the functional effect of two representative isoflavones, genistein and daidzein, on human colonic epithelial cells. The addition of genistein to organoid reformation assays significantly decreased the number and size of reformed hCOs compared with control and daidzein treatment, indicating an inhibitory effect of genistein on colonic cell/progenitor cell function. Evaluation of the phosphorylation status of 49 different receptor tyrosine kinases showed that genistein selectively inhibited phosphorylation of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR). We established a two-dimensional wound-repair model using hCOs and showed that genistein significantly delayed the overall wound-repair response. Our results collectively show that genistein may exert its detrimental effects on the intestinal mucosa via negative regulation of stem/progenitor cell function, possibly leading to sustained mucosal injury and the development of UC. |
Databáze: | OpenAIRE |
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