Altered expression of angiogenic factors in the VEGF-Ets-1 cascades in inflammatory bowel disease.
BACKGROUND
The VEGF-Ets-1 cascades play important roles in angiogenesis by converting endothelial cells to an angiogenic phenotype. The aim of this study was to clarify whether the VEGF-Ets-1 cascades are involved in the pathogenesis of inflammatory bowel disease (IBD).


METHODS
Colonic specimens were taken from 42 patients with ulcerative colitis (UC), 37 with Crohn's disease (CD), 8 with non-IBD colitis, and 21 normal controls. (1) Expression of vascular endothelial growth factor (VEGF), VEGF receptors (Flt-1, KDR), and Ets-1 proteins in colonic mucosa was immunohistochemically examined using specific antibodies. (2) Expression of Ets-1 protein or VEGF, Flt-1, KDR, and Ets-1 mRNA in colonic mucosa was measured by Western blot or RT-PCR.


RESULTS
(1) The number of VEGF-containing cells was significantly increased in active UC ( P <0.05). The numbers of positive blood vessels (mean +/- SE /mm2) to Flt-1, KDR, and Ets-1 antibodies were significantly increased in active UC (Flt-1: 4.0 +/- 0.84; KDR: 2.4 +/- 0.37; Ets-1: 5.5 +/- 0.77) compared to active CD (Flt-1: 0.6 +/- 0.30; KDR: 0.77 +/- 0.28; Ets-1: 2.0 +/- 0.56) ( P <0.01), non-IBD colitis (Flt-1: 1.0 +/- 0.45; KDR: 1.83 +/- 0.54; Ets-1: 3.0 +/- 1.0), and controls (Flt-1: 0.88 +/- 0.40; KDR: 0.60 +/- 0.22; Ets-1: 1.67 +/- 0.47) ( P <0.01). The numbers of positive cells to these antibodies were also increased in active UC. (2) Expression of Ets-1 protein and Flt-1, KDR, and Ets-1 mRNA was increased in active UC.


CONCLUSIONS
Angiogenic factors in the VEGF-Ets-1 cascades were upregulated in UC, but they were relatively downregulated in CD. These alterations might be involved in the pathogenesis of both diseases.
Konno
Shiho
S
Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, 010-8543, Akita, Japan.
Iizuka
Masahiro
M
Yukawa
Michihiro
M
Sasaki
Kenji
K
Sato
Akiko
A
Horie
Yasuo
Y
Nanjo
Hiroshi
H
Fukushima
Tsuneo
T
Watanabe
Sumio
S
D000328:Adult; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D011505:Protein-Tyrosine Kinases