Table 2.
Novel molecular targets and therapy approach identified using intestinal organoids.
| molecular targets | effect | Drug | Species | Ref. |
|---|---|---|---|---|
| Molecular target identified by treatment of intestinal organoids with current therapies for IBD | ||||
| E-cadherin | Re-distribution of protein on intestinal surface restored correct permeability | 5-aminosalycilic acid, azathioprine | Mouse (IL-10−/−) | [134] |
| Desmoglein-2 | Restored physiological desmoglein-2 expression levels | 5-aminosalycilic acid | Mouse (IL-10−/−) | [134] |
| UBD | Restored physiological UBD expression levels | Infliximab | Human (UC patients) | [136] |
| CLDN-2 | Restored physiological CLDN-2 expression levels | Prednisolone, tofacitinib | Human (CD and CRC patients) | [133] |
| ZO-1 | Re-distribution of protein on intestinal surface restored correct | Permeability, Tofacitinib | Human (CRC patients) | [185] |
| Novel potential molecular targets identified using intestinal organoids | ||||
| LRH-1 | Improved resistance to pro-inflammatory mediators and induced mucosal healing | — | Humanized mouse (Lrh-1−/−) LRH-1(+/+) and Human | [186] |
| PXR | Reduced NF-kB activity | — | Human (IBD patients) | [187] |
| IL-22-pSTAT3 SP | Restored tissue damage and intestinal homeostasis | — | Mouse (ATF3−/−) | [188] |
| TGF-β SP | Arrested inflammatory signals | — | Mouse | [189] |
| SIRT2 | Regulated Wnt/β-catenin SP | — | Mouse (Sirt2−/−) | [190] |
| Potential therapeutic approaches for IBD treatment identified using intestinal organoids | ||||
| Sex hormones | Decreased expression of ER stress markers | — | Human (UC female patients) | [191] |
| Naltrexone | Reduced ER stress levels, increased the expression of endogenous encephalins and endorphins | — | Human (IBD patients) | [192] |
| Bacillus subtilis (RZ001) | Promoted intestinal mucosa repair | — | Mouse | [193] |
| Bacterial indoleacrylic acid | Promoted anti-inflammatory cytokines secretion while inducing goblet cells differentiation | — | Mouse | [194] |
| Hyaluronan 35 kDa | Promoted epithelial wound healing | — | Mouse | [195] |
ATF3 Activating transcription factor 3, CD Crohn’s disease, CLDN-2 Claudin-2, CRC Colorectal cancer, ER Endoplasmic reticulum, IBD Inflammatory bowel disease, IL Interleukin, IL-10 Interleukin-10, LRH-1 Liver receptor homolog 1, NF-kB nuclear factor kappa-B, PXR Pregnane X receptor, SIRT2 Human sirtuin protein 2, SP Signaling pathway, STAT Signal transducer and activator of transcription, TGF-βTransforming growth factor-β, UBD Ubiquitin D, UC Ulcerative colitis, ZO-1 Zonula occludens.