Table 1.
Promising Novel Candidates for Therapy of Renal Fibrosis.
| Target | Treatment | Animal model | Outcome | References |
|---|---|---|---|---|
| DDR1 | Gene deletion | Angiotensin II-induced hypertensive nephropathy | Decrease in periglomerular and interstitial fibrosis, inflammation and proteinuria | Flamant et al.12 |
| Gene deletion | UUO (Obstructive nephropathy) | Decreased cytokine expression, reduced macrophage activation, inflammation and fibrosis | Guerrot et al.13 | |
| Gene deletion/antisense administration | NTS-induced glomerulonephritis | Decreased proteinuria and uremia, reduced glomerular crescents, fibrin deposits, inflammation and interstitial fibrosis | Kerroch et al.14 | |
| Antisense administration after initiation of the disease | UUO (obstructive nephropathy), NTS-induced glomerulonephritis | Preserved renal structure and function | Kerroch et al.15 | |
| Gene deletion | Col4a3-/- mice (Alport syndrome) | Increased survival, decreased inflammation and fibrosis, preserved renal function | Gross et al.16 | |
| Gene mutation | 5/6 nephrectomy (chronic renal failure) | Decreased collagen production by mesangial cells | Borza et al.17 | |
| Small molecule inhibitor | NTS- and NEP25-induced glomerulonephritis | Decreased fibrotic and inflammatory gene expression, improved renal function and histology | Moll et al.21 | |
| Periostin | Gene deletion | UUO (obstructive nephropathy) | Decreased cytokine expression, reduced inflammation and fibrosis | Mael-Ainin et al.52 |
| Antisense administration | L-NAME-induced hypertensive nephropathy | Decreased glomerular crescents, tubular dilation, perivascular and interstitial fibrosis, preserved renal function | Mael-Ainin et al.52 | |
| Gene deletion/antisense administration after initiation of the disease | NTS-induced glomerulonephritis | Decreased proteinuria and uremia, reduced glomerular crescents, fibrin deposits, tubular dilation, inflammation and collagen expression | Prakoura et al.53 | |
| Gene deletion | pcy/pcy mice (polycystic kidney disease) | Decreased cyst formation and interstitial fibrosis, preserved renal function | Wallace et al.54 | |
| Blocking antibody | UUO (obstructive nephropathy) | Decreased inflammation, interstitial fibrosis, attenuated TGF-β signaling and apoptosis | Hwang et al.62 | |
| Periostin-binding DNA aptamer | Streptozotocin-induced diabetic nephropathy type 1 or db/db mice (diabetic nephropathy type 2) | Decreased uremia, reduced fibronectin and collagen expression and interstitial fibrosis | Um et al.63 | |
| Adenovirus-shRNA | 5/6 nephrectomy (chronic renal failure) | Decreased renal and cardiac fibrosis, reduced levels of inflammatory and apoptotic markers and improved renal function | Bian et al.57 | |
| Cx43 | Heterozygous mice/antisense administration after initiation of the disease | UUO (obstructive nephropathy), renin overexpression-induced hypertensive nephropathy | Decreased albuminuria, inflammatory cell infiltration and interstitial fibrosis | Abed et al.77 |
| Heterozygous mice/antisense administration after initiation of the disease | NTS-induced glomerulonephritis | Decreased podocyte apoptosis, inflammation and fibrosis, preserved renal function | Kavvadas et al.80 | |
| CB1 | Inverse agonist (rimonabant) | Zucker rat (Diabetic nephropathy type 2) | Decreased serum creatinine, albuminuria and tubulointerstitial lesions | Janiak et al.103 |
| Antagonist (JD5037) | Zucker rat (diabetic nephropathy type 2) | Decreased serum creatinine, albuminuria and tubulointerstitial lesions | Jourdan et al.104 | |
| Inverse agonist (rimonabant) | db/db mice (diabetic nephropathy type 2) | Decreased serum creatinine, albuminuria and mesangial expansion | Nam et al.105 | |
| Antagonist (AM251) | db/db mice (diabetic nephropathy type 2) | Decreased albuminuria and fibronectin expression | Barutta et al.106 | |
| Podocyte-specific deletion | Streptozotocin-induced diabetic nephropathy type 1 | Decreased podocyte injury and apoptosis, reduced tubular damage and interstitial fibrosis | Jourdan et al.107 | |
| Proximal tubule-specific deletion | Obesity-induced CKD | Decreased inflammation, fibrosis and lipid accumulation | Udi et al.109 | |
| Gene deletion/ Inverse agonist (rimonabant) | UUO (obstructive nephropathy) | Decreased inflammation and fibrosis, reduced collagen synthesis | Lecru et al.110 |
Abbreviations: DDR1, discoidin domain receptor 1; UUO, unilateral ureteral obstruction; NTS, nephrotoxic serum; NEP, neuroepithelial tyrosine kinase; Cx43, connexin 43; CB1, cannabinoid receptor 1; CKD, chronic kidney diseases.