Table 2.
miRNA tested in relevant preclinical IBD models for improvement of barrier function and reduction in inflammation.
| Outcome | miRNA | Model | Treatment | Dose and Regimen | Ref |
|---|---|---|---|---|---|
| Occludin upregulation | miR-122a | Intestinal Perfusion Model | Anti-miR-122a | Dose: 25 nM, complexed with Lipofectamine. | [97] |
| miR-200c-3p | 3% DSS | Antagomir-200c-3p | Dose: 800 mg/day, starting two days before DSS treatment and continued for seven days of DSS course; oral gavage. | [101] | |
| miR-21 | miR-21 KO mice, 3.5% DSS | miR-21 deletion showed less susceptibility to DSS induced colitis | N/A | [102] | |
| Claudin CLDN1 upregulation | miR-29a and b | miR-29 KO mice, TNBS | Mice tolerated TNBS induced barrier disruption | N/A | [103] |
| Claudin CLDN8 upregulation | miR-223 | TNBS | Antagomir-223 | Dose: 7.5 mg/kg, prepared as 3 mg/mL in PBS, dosed for three successive days 24 h after TNBS administration; IP administration. | [104] |
| Claudin CLDN11 upregulation | miR-146b-5p | TNBS | antagomir-146b-5p | Not specified | [105] |
| Trefoil factor family 3 (TFF3) upregulation | miR-7 | TNBS | Antagomir-7 | Dose: 100 nmol/kg, tail vein injection, 2 h after TNBS perfusion. | [106] |
| Bcl-2 upregulation | miR-16 | 3% DSS | Anti-miR-16 | Dose: 5 mg/kg IP administration, twice a week, for the two weeks of 3% DSS administration. | [107] |
| Epithelial Regeneration by WNT and Hippo signaling | miR-31 | 3.5% DSS | oxidized konjac glucomannan (OKGM)-PS-miR-31 microspheres | Dose: 3.15 µg, enema. Preventative mode: once per day for 7 d, 2 d gap, 5 d DSS treatment. Therapeutic mode: 5 d DSS treatment, once per day for 7 d; microsphere enema. |
[108] |
| NF-kB pathway dampening | miR-146a | 3% DSS | miR-146a mimics | Dose: 5 mg/kg, IP administration. | [109] |
| miR-214 | DSS | AntagomiR-214 | Dose: 12 mg/kg, 2.5 mg/mL diluted in PBS, 4 doses, every 2 days after DSS treatment regime; intracolonic administration. | [110] | |
| IL10RA activation | miR-142-5p | CD4 + CD45RO + hitransfer | AntagomiR-142-5p | 5 mg/kg, IP, 5 consecutive days starting at 5–10% weight loss; IP | [58] |
| NLRP3 inhibition | miR-223 | 3% DSS | miR-223 mimic | Dose: 50 µg, nanoparticle emulsion- DOPC, squalene oil, PS-20 and an antioxidant, on days 1 and 3 after DSS. | [111] |
| Macrophage polarization | miR-146b | IL-10 KO | miR-146b mimics | Dose: 10 mg/kg, twice a week; IP administration | [112] |
| miR-146b | 3% DSS | miR-146b mimic | Dose: 20 µg/kg, encapsulated in mannose modified trimethyl chitosan nanoparticles; oral administration | [113] | |
| miR-98-5p | 4% DSS | Antagomir-98-5p | Caudal vein administration | [114] | |
| miR-98-5p | TNBS | pcDNA3.1-MEG3 mediated reduction in miR-98-5p | Injected, complexed with Lipofectamine 2000 | [115] | |
| Inhibition of Th1/Th17 mediated inflammatory response | miR-155 | miR-155 KO, 1% DSS | Lower levels of Th17 upon DSS induced colitis observed | N/A | [116] |
| miR-155 | 3% DSS | AntagomiR-155 | Dose: 80 mg/kg, from the 5th day of the DSS cycle, for three consecutive days, IP administration | [117] | |
| miR-31 | TNBS | Antimir-31 | Dose: 5 mg/kg, 12 h after TNBS treatment, complexed with PEI; intracolonic administration | [118] | |
| miR-31 | IL10 KO | Antimir-31 | Dose: 5 mg/kg, weekly for IL10 KO mice, complexed with PEI; intracolonic administration | [118] | |
| miR-301a | TNBS | Anti-miR-301a | Dose: 3 optical density, intracolonic administration daily, starting at the day of TNBS induction till 5 d. | [119] | |
| miR-219a-5p | TNBS | Pre-miR-219a-5p | Dose: 5 mg/kg, complexed with PEI, 4 consecutive days, 12 h after TNBS administration | [120] | |
| Oxidative stress and SBP1 downregulation | miR-122 | TNBS | Pre-miR-122 | Dose: 5 mg/kg, 12 h after TNBS treatment | [121] |
| RhoA reduction | miR-31-3p | 2% DSS | AgomiR-31-3p | Dose: 80 µg; days 1, 3 and 5 of DSS treatment, intracolonic administration | [122] |
DSS: dextran sodium sulfate; TNBS: 2,4,6-trinitrobenzene sulfonic acid; KO: knock out; IP: intraperitoneal; PEI: polyethyleneimine, SBP1: selenium binding protein 1; DOPC: 1,2-dioleoyl-sn-glycero-3-phosphocholine; PS-20: polysorbate-20.