Table 3.
Table showing the major cytokines, growth factors, chemokines, enzymes and cytoskeletal proteins which demonstrate altered intra-renal regulation in obstructive nephropathy, the timing of these changes and their mode of action
| Proteina | Action | Change/timing | Species | Reference |
|---|---|---|---|---|
| Angiotensin II | Vasoregulatory, proinflammatory, proapoptotic, profibrotic | Increased 28 days Increased 1 week and 5 weeks Increased after mechanical stretch |
Neonatal rat CUUO Adult rat CUUO In vitro podocytes |
[63] [64] [65] |
| α-SMA | Increases myofibroblast contractility/EMT marker | Increased 5 days Increased 4 days |
Neonatal rat CUUO Adult mouse CUUO |
[39] [66] |
| Caspases | Proapoptotic | Increased 14 days Increased 1 day |
Neonatal rat CUUO Adult rat CUUO |
[67] [68] |
| Clusterin | Cytoprotective via pro-survival autophagy | Increased 5 days | Neonatal rat CUUO | [39] |
| COX-2 | Polyuria and natriuresis, anti-apoptotic, antifibrotic | Increased 24 h Increased 3 days (mRNA) |
Adult rat CBUO Adult mouse CUUO |
[69] [70] |
| CTGF | Profibrotic | Increased 2 days (mRNA) | Adult rat CUUO | [45] |
| EGF | Epithelial survival factor | Decreased 7 days (mRNA) (Undetectable expression in neonatal rat kidney before 4 days) Decreased 33 days Decreased at pyeloplasty (mean age 2 years) (mRNA) Decreased at pyeloplasty (mean age 5 years) |
Neonatal rat CUUO Neonatal rat both CUUO and 5 day CUUO then release Human renal biopsy Human renal biopsy |
[71] [39] [72] [73] |
| ET-1 | Vasoconstrictor | Increased 2 days (mRNA) | Adult rat CUUO | [45] |
| Fas-L | Proapoptotic | Increased 1 day (mRNA) | Adult rat CUUO | [68] |
| HSP-70 | Antiapoptotic | Decreased 14 days | Neonatal CUUO | [67] |
| ICAM-1 | Proinflammatory | Increased 3 days | Adult mouse CUUO | [74] |
| Il-6 | Proinflammatory | Increased 2 days (mRNA) | Adult rat CUUO | [45] |
| Integrin (β1) | Profibrotic | Increased 3 days Increased after mechanical stretch |
Adult mouse CUUO In vitro proximal tubular cells |
[75] [76] |
| MCP-1 | Proinflammatory | Increased 12 days, no change 4 days Increased 2 days (mRNA) Increased at pyeloplasty (mean age 2 years) (mRNA) |
Neonatal rat CUUO Adult rat CUUO Human renal biopsy |
[77] [45] [72] |
| MMP 2 and 9 | ECM degradation | Decreased 3 days | Adult mouse CUUO | [74] |
| PAI-1 | Profibrotic, inhibits ECM degradation | Increased 7 days | Adult mouse CUUO | [78] |
| PDGF | Profibrotic | Increased 4 days | Adult mouse CUUO | [66] |
| NF-κB | Regulatory transcription factor | Increased 2 days | Adult mouse CUUO | [45] |
| Nitric oxide | Vasodilator, anti-apoptotic, antifibrotic | Decreased 14 days | Neonatal rat CUUO | [67, 79] |
| Renin | Cleaves angiotensinogen, upregulates renin–angiotensin system | Increased 3 days (mRNA) Increased 5 days Increased 14 days (mRNA) Increased 4–5 weeks Increased 24 h Increased after mechanical stretch |
Neonatal rat CUUO Neonatal rat CUUO Neonatal rat CUUO Neonatal rat CUUO Adult rat CUUO In vitro proximal tubular cells |
[71] [39] [63] [80] [81] [82] |
| TGF-β | Proinflammatory, proapoptotic, profibrotic, stimulates EMT | Increased 1 day (mRNA) Increased 33 days Increased 3 days (mRNA) Increased at pyeloplasty (mean age 5 years) |
Neonatal rat CUUO Neonatal rat both CUUO and 5 day CUUO then release Adult rat CUUO Human renal biopsy |
[71] [39] [83] [73] |
| TIMP-1 | Profibrotic, inhibits ECM degradation | Increased 5 days Increased 3 days |
Adult rat CUUO Adult mouse CUUO |
[84] [74] |
| TNF-α | Proapoptotic, proinflammatory | Increased 14 days (mRNA) Increased 1 day Increased 2 days (mRNA) Increased 1 day |
Neonatal rat CUUO Adult rat CUUO Adult rat CUUO Adult rat CUUO |
[85] [68] [45] [68] |
| VCAM-1 | Proinflammatory | Increased 3 days (mRNA) | Adult mouse CUUO | [86] |
| VEGF (podocytes) | Endothelial survival factor | Increased 28 days Decreased 14 days |
Neonatal PUUO Neonatal CUUO |
[87] [87] |
| VEGF (tubules) | Endothelial survival factor | Variable expression Decreased 14 days |
Neonatal PUUO Neonatal CUUO |
[87] [87] |
| Vimentin | Intermediate filament protein/ EMT marker | Increased 5 days | Neonatal rat CUUO | [39] |
| WT-1 | Transcriptional regulator, key role in renal development | Decreased 14 days | Neonatal rat CUUO | [85] |
Change is compared to sham animal or control human kidney and refers to protein expression unless otherwise stated. Timing is days after creation of unilateral ureteric obstruction (UUO)
CUUO, Complete UUO; CBUO complete bilateral ureteric obstruction; PUUO, partial UUO
aα-SMA, Alpha-smooth muscle actin; COX-2, cyclooxygenase 2; CTGF, connective tissue growth factor; ECM, extracellular matrix; EGF, epidermal growth factor; EMT, epithelial–mesenchymal transition; FasL, Fas ligand; HSP-70, heat shock protein 70; ICAM-1, intercellular adhesion molecule 1; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein 1; MMP, matrix metalloproteinase; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TGF-β, transforming growth factor-beta; TIMP-1, tissue inhibitor of metalloproteinases 1; TNF-α , tumour necrosis factor-alpha; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor; WT-1, Wilms tumor protein