Table 1.
Targeting IEC modulators or signaling pathways to treat IBD.
| Modulators/pathways | Mode of action | Biological process | References |
|---|---|---|---|
| Creatine transporter protein SLC6A8 | Promote expression and localization of tight junction proteins Claudin1/2 and actin polymerization | Regulate energy balance and maintain barrier formation and healing function | Hall et al. (2020) |
| Golgi membrane protein 1 (GOLM1) | Regulate the balance of the Notch signaling pathway | Maintain barrier homeostasis | Pu et al. (2021) |
| Myosin light chain kinase splice variant (MLCK1) | TNF-induced MLCK1 recruitment to peri-junctional actomyosin ring (PAMR) mediates MLC phosphorylation. | Maintain barrier function | Graham et al. (2019) |
| Interact with FKBP8 PPIase for MLCK1 recruitment and MLC phosphorylation | |||
| miR-181 family members | Regulate Wnt and immune processes | Promote intestinal recovery after injury | Jimenez et al. (2022) |
| Histone H3K9 methyltransferase SETDB1 | Silence endogenous retroviruses to inhibit DNA damage | Maintain IECs survival, barrier function, and homeostasis | Juznic et al. (2021) |
| m6A methyltransferase METTL14 | Regulate NF-kB mRNA stability, affecting the activity of the NF-kB pathway and inhibiting TNF-mediated apoptosis | Regulate the development and apoptosis of colonic epithelial cells and colonic stem cells | Zhang et al. (2022) |
| DNA methyltransferase 3A (DNMT3A) | DNMT3A deficiency leads to hypomethylation | Maintain intestinal epithelial barrier function and regeneration | Fazio et al. (2022) |
| Special AT-rich sequence-binding protein 2 (SATB2) | Increase the expression of the Cl-/HCO3-transport protein SLC26A3 | Maintain diversity and composition of the gut microbiota | Ni et al. (2021) |
| 5-Hydroxytryptamine (5-HT) | Reduce TGF-β secretion and inhibit the TGF-β/SMAD pathway | Tumor-suppressive effects at the initiation stage of CAC | Mao et al. (2022) |
| Enhance AKT activity through 5-HT2B and activate the IL-6/STAT3 pathway | Promote tumor progression in the later stages of CAC | ||
| Spermidine oxidase (SMOX) | Promote spermidine production and inhibit alpha-defensin expression | Maintain diversity and composition of the gut microbiota | Gobert et al. (2022) |
| Stromal interaction molecule 1 (STIM1) | STIM1 deficiency controls the stimulation of the intestinal epithelium by reducing endoplasmic reticulum stress caused by an imbalance in Ca2+ homeostasis | Maintain intestinal barrier | Liang et al. (2022) |
| RhoB | Reduced or absent RhoB inhibits the Wnt pathway and activates the p38 MAPK pathway | Promote goblet cell differentiation and IECs proliferation, increase SCFA-producing bacteria abundance and elevate the levels of SCFAs and receptors | Yang et al. (2022) |
| Leukemia inhibitory factor (LIF) | Inhibit Th17 cells differentiation by phosphorylating and activating STAT4 and suppressing STAT3-induced IL17 gene expression | Alleviate colonic inflammation | Zhang et al. (2019) |
| Alpha B-crystallin (CRYAB) | Reduce cellular inflammatory factor (TNF-α, IL-6, IL-1β, IL-8) production by inhibiting IKKβ activity | Protect barrier integrity | Xu et al. (2019) |
| deSUMOylase SENP7 | Ubiquitin ligase SIAH2 downregulates SENP7 through ubiquitination, which reduces pro-inflammatory mechanisms through γδ T cells. | Control intestinal inflammation | Suhail et al. (2019) |
| Epithelial NF-κB2 signaling | Amplify RelA activity and increase RelA-driven inflammatory gene expression | Induce abnormal intestinal inflammation | Chawla et al. (2021) |
| Guanylate cyclase C (GC-C) | Regulate intestinal ion and fluid secretion through cGMP production and activation of cGMP-dependent protein kinase II | Loss of overall internal environmental homeostasis, fluid ion imbalance, and dysregulation of the intestinal microbiota | Mishra et al. (2021) |
| Epithelial autonomous NAIP/NLRC4 inflammasomes | Drive IEC pyroptosis or apoptosis and promote IEC expulsion | Mitigate TNF-induced disruption of the intestinal epithelial barrier | Fattinger et al. (2021) |
| NLRP3 Inflammasomes | miR223 mediates NLRP3 regulation and NLRP3 pathway blockage reduces IL-1β production | Inhibition of inflammasomes suppresses excessive inflammatory responses in the intestine | Kanneganti (2017) |
| ADP/P2Y1 | ADP activates NLRP3 inflammasomes via P2Y1 receptors and promotes NLRP3 inflammasomes component ASC phosphorylation to increase IL-1β production | Zhang et al. (2020) | |
| NLRP6 inflammasomes | Deubiquitinating enzyme Cyld binds to NLRP6, removes its ubiquitination modifications, inhibits NLRP6-ASC inflammasome formation, and regulates the maturation process of IL-18. | Mukherjee et al. (2020) | |
| Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX1) | The absence of intestinal epithelial NOX1 combined with TNFα stimulation alters the stem cell microenvironment and stem cell differentiation | Promote lymphoplasmacytosis | Hsu et al. (2022) |
| Superoxide dismutase 1 (SOD1) | Restoring SOD activity inhibits p38-MAPK/NF-κB signal-mediated inflammation and apoptosis. | SOD1 deletion enhances oxidative stress and disrupts the intestinal epithelial barrier, reduces antioxidant enzyme activity, and increases colonic infiltration of pro-inflammatory immune cells | Hwang et al. (2020) |
| Multidrug resistance 1 (MDR1) | Reduce mROS | Protect mitochondria against xenotoxins through its efflux function | Ho et al. (2018) |
| 3-mercaptopyruvate sulfurtransferase (MPST) | Regulate the AKT/apoptotic axis in IECs, inhibit pro-inflammatory cytokines expression, ROS production | Protect the intestine from inflammation and apoptosis incidence | Zhang et al. (2022) |
| Reductively modified albumin (r-Alb) | Inhibit cellular ROS and superoxide production through sulfhydryl (-SH) | Reduce the cellular damage caused by oxidative stress | Yang et al. (2021) |