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Functional analysis of isoflavones using patient-derived human colonic organoids
- Source :
- Biochemical and Biophysical Research Communications. 542:40-47
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 542
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....8a4a1988443cedb70cc0c9c58c3ddc38