Table 1.
Potential therapeutic targets in obstructive nephropathy
| Molecule | Targeting technique | Effect | Ref |
|---|---|---|---|
| RAS system | |||
| AT1 | receptor antagonist | Combination with AT2 antagonist decreased inflammation | 30 |
| KO | no effect | ||
| AT2 | receptor antagonist | Combination with AT1 antagonist decreased inflammation | 30 |
| KO | Increased fibrosis | 122 | |
| Kinin B1 receptor | receptor antagonist | Decreased inflammation and fibrosis | 151 |
| MAS (Ang-(1–7) receptor) | KO | Decreased inflammation and fibrosis | 126 |
| ACE | pharmacological inhibition | Decreased inflammation and fibrosis | 123 |
| Inflammation | |||
| NFκB | NF-κB decoy double-stranded ODN |
Decreased NFκB activation and inflammation | 148 |
| pharmacological inhibition | DHMEQ, PDCT and parthenolide decrease inflammation and fibrosis | 30,147 | |
| TNFα receptors 1 and 2 | KO | Decreased inflammation | 127 |
| TNFα | antibody neutralization | Decreased NFκB activation and inflammation | 149 |
| CCR2 and CCR1 | pharmacological inhibition | Decreased inflammation and fibrosis | 152,154,155 |
| KO | Decreased inflammation and fibrosis | 152,154,155 | |
| OPN | KO | Decreased inflammation | 156 |
| MCSF-1 | receptor antagonist | Decreased inflammation | 51 |
| CCL21/CCR7 | CCL21 antibody neutralization CCR7 KO |
Decreased fibrosis and inflammation | 74 |
| TGF-β1 | |||
| TGF-β1 | antibody neutralization | Decreased apoptosis | 129 |
| BMP-7 | administration | Decreased inflammation and may decrease fibrosis | 91 |
| Decorin | KO | Increased tubular apoptosis and atrophy | 135 |
| Smad3 | KO | Decreased fibrosis, inflammation, and apoptosis | 133 |
| KO | Decreased fibrosis (decreased EMT and ECM) | 132 | |
| Smad7 | transgenic mice overexpression | Decreased inflammation and NFκB inhibition | 134 |
| EPO | administration | Decreased fibrosis (decreased EMT) | |
| Plasminogen/plasmin system | |||
| tPA | KO | Decreased EMT, preservation of the integrity of tubular basement membranes | 142 |
| PAI-1 | transgenic mice overexpression | Increased inflammation and fibrosis | 143 |
| KO | Decreased inflammation and fibrosis | 144 | |
| Other | |||
| ET-1 | receptor antagonist | Decreased tubular apoptosis, restoration of blood flow | 31 |
| PTHrP | transgenic mice overexpression | Increased inflammation | 150 |
| receptor antagonist | Decreased inflammation | ||
| CDK | pharmacological inhibition | Decreased tubular cell proliferation and apoptosis | 158 |
| iNOS | KO | Conflict results | |
| Increased inflammation and fibrosis | 96 | ||
| Decreased fibrosis (through other NOS isoforms) | 141 | ||
| L-arginine | administration | Decreased fibrosis (Induces NO) | 139 |
Notes: Bolded text in Effect column = interventions with negative consequences.
Abbreviations: KO, knock-out; TNF, tumor necrosis factor; ACE, angiotensin-converting enzyme; NF-κB, nuclear transcription factor-kappaB; OPN, osteopontin; MCSF-1, macrophage colony-stimulating factor-1; TGF-β1, transforming growth factor-β1; BMP-7, bone morphogenetic protein-7; EPO, erythropoietin; PAI-1, plasminogen activator; inhibitor-1; RAS, renin-angiotensin-aldosterone system; ET-1, endothelin-1; PTHrP, parathyroid hormone-related protein; iNOS, inducible nitric oxide synthase.