Table 1.
Approaches to anti-fibrotic therapies in preclinical studies.
| Type | Target | References |
|---|---|---|
|
| ||
| TGF-β antagonists | Anti TGF-β antibodies | stz-induced diabetes (30), db/db mice (31, 32), salt-sensitive hypertension (33, 34) |
| Pirfenidone (inhibits TGF-β synthesis) | UUO (38) subtotal nephrectomy (39-41) db/db mice (42) |
|
| Tranilast analogs: FT011, FT061 | stz-induced diabetes (52,53) subtotal nephrectomy (53) UUO (58) |
|
| Smad7 overexpression (gene transfer) | crescentic glomerulonephritis (59) subtotal nephrectomy (60) |
|
| TAK1 inhibition | Tak 1 deficient mice (61) | |
| TGF-β receptor antagonist:GW788388 | db/db mice (63) | |
| TβR-ll siRNA | UUO (64) | |
|
| ||
| BMP-7 agonists | rhBMP-7 | nephrotoxic serum nephritis (85) UUO (86, 87) stz-induced diabetes (88, 89) MRL/MpJ/pr/lpr lupus mice (90) |
| BMPR agonists: THR-123, THR-184 | nephrotoxic nephritis, stz-induced diabetes (95, 96) | |
| Kielin/chordin-like protein | UUO, folic acid-induced ATN (97) | |
| Inhibition of USAG-1 or gremlin | UUO, model of Alport syndrome, stz-induced diabetes (98-101) | |
|
| ||
| CTGF inhibitors | Antisense oligonucleotides | UUO (110) TGF-β transgenic mice (111) |
| CTGF siRNA | stz-induced diabetes, db/db mice (113) | |
| Anti-CTGF antibody (FG-3019) | stz-induced diabetes, db/db mice (115) | |
|
| ||
| CCL2-CCR2 and CCR1 inhibitors | CCR2 antagonists: propagermanium, RS-504393 | stz-induced diabetes (124) db/db mice (125) UUO (127) |
| CCR2 antagonist: CCX140-B | high-fat fed and db/db mice (126) | |
| CCR1 antagonist: BX471 | nephrotic syndrome, FSGS (132) lupus-like nephritis (133) UUO (134) |
|
|
| ||
| PDE inhibitors | Pentoxifylline | UUO (135) 5/6 subtotal nephrectomy (136) crescentic glomerulonephritis (137) |
| Vardenafil | alloxan-induced diabetic rabbits (141) | |
| Sildenafil | stz-induced diabetes (142) | |
|
| ||
| Nox1/4 inhibitor | GKT137831 | db/db mice (144) |
|
| ||
| ET-1 antagonists | ETA receptor blocker: FR139317 | hypertensive rat (156) |
| ETA receptor blocker: atrasentan | hypertensive Ren-2 transgenic rats (157) | |
| Non selective ET blocker: bosentan | L-NAME treated mice (158) | |
|
| ||
| TNF-α antagonists | Anti-TNF-α antibody | crescentic glomerulonephritis (162) |
Abbreviations; ATN, acute tubular necrosis; BMP, bone morphogenic protein; BMPR, BMP receptor; CCL2-CCR2, CC motif chemokine ligand 2- CC receptor type 2; CCR1, CC receptor type 1 ; CTGF, connective tissue growth factor; ET, endothelin; FSGS, focal segmental glomerular sclerosis; L-NAME, NG-nitro-L-arginine methylester; Nox, NADPH oxidase ; PDE, phosphodiesterase ; stz, streptozotocin; TGF-β, transforming growth factor-β; TNF-α, tumor necrosis factor-α.