Collagenous colitis: implications for the role of vascular endothelial growth factor in repair mechanisms.
OBJECTIVE
Collagenous colitis is a chronic inflammatory bowel disease with a band-like subepithelial deposition of immature extracellular matrix. Because the extracellular matrix deposition is potentially reversible, an imbalance between fibrogenesis and fibrolysis with reduced matrix degradation has been suspected. Vascular endothelial growth factor plays a central role in extracellular matrix degradation. Therefore, we investigated the expression of vascular endothelial growth factor in the colonic mucosa of patients with collagenous colitis before and after long-term treatment with oral budesonide.


METHODS
A quantitative immunohistochemical method was used to measure the amount of immunoreactive vascular endothelial growth factor, tenascin and leucocyte common antigen within the epithelium and the lamina propria of colonic biopsies by area morphometry.


RESULTS
Strong immunostaining for vascular endothelial growth factor within the epithelium and the lamina propria, and for tenascin, was seen in patients with collagenous colitis compared with normal controls. The enhanced immunostaining for vascular endothelial growth factor within the lamina propria was accompanied by the accumulation of leucocytes, detected by staining for leucocyte common antigen. After long-term treatment with oral budesonide, the amount of immunostaining for leucocyte-derived vascular endothelial growth factor within the lamina propria decreased significantly to normal levels. In contrast, staining for vascular endothelial growth factor within the epithelium remained significantly increased.


CONCLUSIONS
Our data suggest an important role of vascular endothelial growth factor in counteracting the local imbalance of fibrogenesis and fibrolysis, leading to an accumulation of immature subepithelial matrix in collagenous colitis.
Griga
Thomas
T
Department of Gastroenterology, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany. thomas.griga@ruhr-uni-bochum.de
Tromm
Andreas
A
Schmiegel
Wolff
W
Pfisterer
Okka
O
Müller
Klaus-M
KM
Brasch
Frank
F
D000284:Administration, Oral; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism*; D003094:Collagen; D003106:Colon / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D019063:Tenascin / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D019063:Tenascin; D042461:Vascular Endothelial Growth Factor A; D019819:Budesonide; D003094:Collagen; D017493:Leukocyte Common Antigens