Gene expression profiling and functional analysis of angiogenic markers in murine collagen-induced arthritis

Raatz, Yvonne; Ibrahim, Saleh; Feldmann, Marc; Paleolog, Ewa M

doi:10.1186/ar3922

Arthritis Research & Therapy

Table 2 Angiogenesis-related genes altered during the course of acute CIA

From: Gene expression profiling and functional analysis of angiogenic markers in murine collagen-induced arthritis

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.

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