Table 1.
Preclinically tested approaches for intestinal fibrosis in animal models based on antifibrotic clinical trials in other organs
| Model System | Mechanism | Prevention or Reversal of Fibrosis | Effects | Year | Reference | |
|---|---|---|---|---|---|---|
| TGF-β1 vaccination | Murine chronic TNBS-induced colitis | TGF-β1 antagonism | Both preventive and reversal (from week 0 or 2 of TNBS colitis) | Reduced collagen deposition and decreased levels of TGF-β1, IL-17, and IL-23 | 2010 | (127) |
| Smad7-specific antisense oligonucleotide | Murine chronic TNBS-induced colitis | TGF-β1 signaling modulator | Reversal (from week 5 or 9 of TNBS colitis) | Reduced signs of colitis, reduced collagen deposition, and diminished fibrosis | 2018 | (134) |
| Pirfenidone | Murine chronic DSS-induced colitis | TGF-β, TNF-α, and NF-κB modulator | Both preventive and reversal (from day 0 or 14 of DSS colitis) | Reduced collagen deposition, suppressed the mRNA expression of COL1A2, COL3A1, and TGF-β | 2016 | (129) |
| IL-10 | Spontaneous colitis of IL-10 knockout mice | IL-10 administration | Preventive (from week 12 of age) | Decreased tissue fibrosis, decreased inflammatory cytokines and TGF-β1 | 2013 | (230) |
| IL-13 receptor α2-specific small interfering RNA | Murine chronic TNBS-induced colitis | IL-13 inhibitor | Therapeutic (from day 35 of TNBS colitis) | Alleviated fibrosis and TGF-β1 production | 2007 | (232) |
| IL-36 receptor antibody | Murine chronic DSS- and TNBS-induced colitis | IL-36 inhibitor | Preventive (from day 1 of DSS or TNBS colitis) | Reduced fibrosis score, submucosal thickness, and α-SMA-positive cells | 2019 | (172) |
| AMA0825 | Murine chronic TNBS-induced colitis and adoptive T-cell transfer colitis | Local ROCK inhibitor | Both preventive and reversal (from week 2 of T-cell transfer or week 7 of DSS colitis) | Inhibited myofibroblast accumulation, expression of profibrotic factors, and accumulation of fibrotic tissue; reversed established fibrosis | 2017 | (365) |
| GED-0507-34 Levo | Murine chronic DSS-induced colitis | 5-ASA analog (mimicked by PPAR-γ) | Preventive (from day 12 of DSS colitis) | Improved macroscopic and microscopic intestinal lesions; reduced the profibrotic gene expression of ACTA2, COL1A1, and FN1; reduced protein levels of α-SMA and collagen I/II, TGF-β/Smad pathway components, IL-13, and CTGF | 2016 | (369) |
| GED-0507-34 Levo | Murine chronic DSS-induced colitis | 5-ASA analog (mimicked by PPAR-γ) | Preventive (from day 12 of DSS colitis) | Reduced the expression of the main fibrosis markers (α-SMA, collagen I–III, and fibronectin) as well as the pivotal profibrotic molecules IL-13, TGF-β and Smad3; increased the antifibrotic PPAR-γ | 2017 | (368) |
| LOX inhibitor | Murine chronic DSS-induced colitis | LOX inhibitor | Preventive (from day 0 of DSS colitis) | Reversed the ECM contraction and MMP3 activity in stenotic myofibroblasts grown in fibrotic environment | 2018 | (47) |
| Captopril | Murine chronic TNBS-induced colitis | ACEI | Preventive (from day 0 of TNBS colitis) | Reduced the score of macroscopic and histological lesions, colonic tissue levels of collagen α1, hydroxyproline, ANG II, and TGF-β1 proteins, and TGF-β1 mRNA | 2004 | (410) |
| Losartan | Murine chronic TNBS-induced colitis | ARB | Preventive (from day 0 of TNBS colitis) | Improved macro- and microscopic scores of intestinal fibrosis and reduced TGF-β1 concentration | 2012 | (411) |
| Simvastatin | Murine chronic TNBS-induced colitis | HMG-CoA reductase inhibitor | Preventive (from day 2 of TNBS colitis) | Attenuated intestinal fibrosis by lowering CTGF and inducing apoptosis of fibroblasts and myofibroblasts | 2012 | (442) |
ACEI, angiotensin-converting enzyme inhibitor; ANG, angiotensin; ARB, angiotensin II receptor blocker; 5-ASA, 5-aminosalicylic acid; CTGF, connective tissue growth factor; DSS, dextran sulfate sodium; ECM, extracellular matrix; HMG-CoA, 5-hydroxy-3-methylglutaryl-coenzyme A; IL, interleukin; LOX, lysyl oxidase; MMP, matrix metalloproteinase; NF, nuclear factor; PPAR, peroxisome proliferator activator receptor; ROCK, rho-associated coiled-coil forming protein kinase; α-SMA, α-smooth muscle actin; TGF, tumor growth factor; TNBS, 2,4,6-trinitrobenzenesulfonic acid solution; TNF, tumor necrosis factor.