Table 2.
Angiogenesis-related genes altered during the course of acute CIA
| Gene | Gene bank | Gene name | Onset | Day 4 | Day 8 | Day 12 | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Fold change | P-value | Fold change | P-value | Fold change | P-value | Fold change | P-value | |||
| Growth factors and receptors | ||||||||||
| Ang-1 | NM_009640 | Angiopoietin 1 | 1.3 | 1.8 | 2.7 | 0,004 | 1.5 | |||
| Edg1 | NM_007901 | Endothelial differentiation sphingolipid G-protein-coupled receptor 1 | 1.8 | 2.4 | 0,001 | 3.3 | 0,002 | 2.4 | 0,005 | |
| Egf | NM_010113 | Epidermal growth factor | -1.4 | -2.9 | 0,013 | -3.7 | 0,005 | -2.9 | 0,005 | |
| Ereg | NM_007950 | Epiregulin | -1.4 | -2.1 | 0,001 | -2.3 | 0,002 | -1.8 | ||
| Fgf-1 | NM_010197 | Fibroblast growth factor 1 | -1.3 | -2.3 | 0,004 | -1.7 | -1.1 | |||
| Flk-1 | NM_010612 | Fetal liver kinase | 1.3 | 2.2 | 0,011 | 3.0 | 0,006 | 1.9 | ||
| Hgf | NM_010427 | Hepatocyte growth factor | 2.2 | 0,006 | 4.6 | 0,001 | 6.0 | 0,001 | 3.9 | 0,002 |
| Igf-1 | NM_010512 | Insulin-like growth factor 1 | 1.4 | 2.4 | 0,000 | 4.1 | 0,001 | 2.4 | 0,000 | |
| Lep | NM_008493 | Leptin | -2.5 | 0,007 | -5.8 | 0,002 | -6.8 | 0,002 | -3.9 | 0,015 |
| Mdk | NM_010784 | Midkine | 1.5 | 2.4 | 0,008 | 7.5 | 0,002 | 5.3 | 0,003 | |
| Nrp-2 | NM_010939 | Neuropilin 2 | 1.4 | 2.0 | 0,009 | 2.4 | 0,015 | 2.2 | 0,011 | |
| Tgfβ1 | NM_011577 | Transforming growth factor, beta 1 | 1.6 | 2.1 | 0,009 | 2.3 | 0,005 | 1.8 | ||
| Tgfβ2 | NM_009367 | Transforming growth factor, beta 2 | -1.4 | -2.0 | 0,021 | -1.3 | 1.1 | |||
| Tgfβr1 | NM_009370 | Transforming growth factor, beta receptor I | 1.5 | 1.6 | 2.0 | 0,003 | 1.5 | |||
| Proteases and inhibitors | ||||||||||
| Mmp-2 | NM_008610 | Matrix metallopeptidase 2 | 1.7 | 2.6 | 0,001 | 4.1 | 0,000 | 3.0 | 0,001 | |
| Mmp-9 | NM_013599 | Matrix metallopeptidase 9 | 3.4 | 0,002 | 16.2 | 0,001 | 20.2 | 0,001 | 12.7 | 0,001 |
| Mmp-19 | NM_021412 | Matrix metallopeptidase 19 | 3.6 | 0,001 | 4.6 | 0,002 | 5.2 | 0,000 | 3.8 | 0,003 |
| Timp-1 | NM_011593 | Tissue inhibitor of metalloproteinase 1 | 17.1 | 0,009 | 34.0 | 0,001 | 24.4 | 0,001 | 11.6 | 0,001 |
| Timp-2 | NM_011594 | Tissue inhibitor of metalloproteinase 2 | 1.2 | 1.4 | 2.4 | 0,001 | 2.1 | 0,001 | ||
| Adhesion molecules | ||||||||||
| Cdh5 | NM_009868 | Cadherin 5 | 1.6 | 3.0 | 0,003 | 3.5 | 0,002 | 2.3 | 0,017 | |
| Eng | NM_007932 | Endoglin | 1.6 | 1.9 | 2.6 | 0,007 | 1.9 | |||
| Itgβ3 | NM_016780 | Integrin beta 3 | 1.9 | 5.9 | 0,001 | 6.1 | 0,001 | 3.4 | 0,001 | |
| Pecam1 | NM_008816 | Platelet/endothelial cell adhesion molecule 1 | 1.7 | 1.7 | 2.1 | 0,012 | 1.8 | |||
| Stab1 | NM_138672 | Stabilin 1 | 2.6 | 0,000 | 4.0 | 0,001 | 3.3 | 0,001 | 2.0 | 0,002 |
| Transcription factors | ||||||||||
| Efnβ2 | NM_010111 | Ephrin B2 | -2.0 | -2.5 | 0,001 | -1.7 | -1.1 | |||
| Hif-1α | NM_010431 | Hypoxia inducible factor 1, alpha subunit | 1.5 | 2.6 | 0,001 | 3.8 | 0,000 | 1.6 | ||
| Tbx1 | NM_011532 | T-box 1 | -1.7 | -3.3 | 0,003 | -3.3 | 0,011 | -2.0 | 0,013 | |
| Tnfαip2 | NM_009396 | Tumor necrosis factor, alpha-induced protein 2 | 2.0 | 0,002 | 2.6 | 0,004 | 2.6 | 0,001 | 2.0 | 0,001 |
| Anti-angiogenic factors | ||||||||||
| Tsp-1 | NM_011580 | Thrombospondin 1 | 1.8 | 1.9 | 2.8 | 0,000 | 2.0 | 0,006 | ||
| Tsp-2 | NM_011581 | Thrombospondin 2 | 1.3 | 2.2 | 0,003 | 2.9 | 0,001 | 2.0 | 0,002 | |
| Col4α3 | NM_009929 | Procollagen, type IV, alpha 3/tumstatin | 1 | -2.0 | 0,015 | -2.0 | 0,011 | -1.3 | ||
| Col18α1 | NM_007734 | Procollagen, type XVIII, alpha 1/endostatin | 1.1 | 1.7 | 2.0 | 0,012 | 2.0 | 0,015 | ||
| Cytokinesand chemokines | ||||||||||
| Il-1β | NM_008361 | Interleukin 1 beta | 34.1 | 0,000 | 48.2 | 0,000 | 60.0 | 0,000 | 16.2 | 0,000 |
| Il-6 | NM_031168 | Interleukin 6 | 183.7 | 0,000 | 190.4 | 0,000 | 164.7 | 0,000 | 30.3 | 0,001 |
| Tnfα | NM_013693 | Tumor necrosis factor | 2.2 | 0,014 | 2.2 | 0,009 | 3.7 | 0,010 | 2.2 | 0,018 |
| Ccl2 | NM_011333 | Chemokine (C-C motif) ligand 2/MCP1/HC11 | 15.0 | 0,000 | 11.0 | 0,001 | 10.0 | 0,000 | 3.0 | 0,001 |
| Cxcl1 | NM_008176 | Chemokine (C-X-C motif) ligand 1/Gro1 | 19.2 | 0,003 | 35.7 | 0,001 | 21.0 | 0,001 | 7.0 | 0,019 |
| Cxcl2 | NM_009140 | Chemokine (C-X-C motif) ligand 2/Grob | 8.7 | 0,001 | 13.4 | 0,001 | 15.2 | 0,001 | 6.1 | 0,001 |
| Cxcl5 | NM_009141 | Chemokine (C-X-C motif) ligand 5/ENA-78 | 126.3 | 0,002 | 378.4 | 0,001 | 345.8 | 0,001 | 70.3 | 0,003 |
| Ccl11 | NM_011330 | Small chemokine (C-C motif) ligand 11/eotaxin | 1.1 | -2.0 | 0,003 | -2.0 | 0,019 | 1.2 | ||
| Csf3 | NM_009971 | Colony stimulating factor 3 (granulocyte)/G-CSF | 86.9 | 0,016 | 69.7 | 0,017 | 48.9 | 0,020 | 20.3 | 0,034 |
Angiogenesis RT2-Profiler PCR arrays (APM-024; SuperArray Bioscience, Frederick, MD) were performed using cDNA from paws of CIA mice at different time points post-arthritis onset. For each time point, RNA from four animals was pooled and analysed in duplicate. Data are expressed as fold change relative to the expression in paws from healthy mice after normalisation to four housekeeping genes. The table lists genes that exhibit at least a two-fold difference in expression at one or more time-points in arthritic tissue when compared to control tissue. Data were analysed by paired t-test.