TY - JOUR
T1 - Up-Regulation of Collagen and Tissue Inhibitors of Matrix Metalloproteinase in Colonic Diverticular Disease
AU - Mimura, Toshiki
AU - Bateman, Adrian C.
AU - Lee, Ronald L.
AU - Johnson, Penelope A.
AU - McDonald, Peter J.
AU - Talbot, Ian C.
AU - Kamm, Michael A.
AU - MacDonald, Thomas T.
AU - Pender, Sylvia L.F.
AU - Koltun, Walter
N1 - Funding Information:
Supported by the Innovation Fund, Hope, Wessex Medical Trust, Southampton, United Kingdom.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/3
Y1 - 2004/3
N2 - PURPOSE: Thickening of the muscularis propria is a key pathologic feature of colonic diverticulosis but its cause is unknown. This study was designed to investigate the role of collagens, matrix metalloproteinases, and tissue inhibitor of metalloproteinases in colonic diverticulosis. METHODS: Collagen content was determined by Sircol Collagen Assay and standard van Gieson staining. Messenger-RNA expression for matrix metalloproteinases and tissue inhibitor of metalloproteinase was analyzed by quantitative competitive reverse transcription polymerase chain reaction. Immunohistochemical staining was performed to localize tissue inhibitor of metalloproteinases in sections. RESULTS: In mucosa and submucosal layer, complicated diverticular disease samples had a higher collagen content than uncomplicated disease, which in turn had higher levels than controls. There was an 18-fold increase in tissue inhibitor of metalloproteinase-1 mRNA, and a threefold increase in tissue inhibitor of metalloproteinase-2 mRNA in complicated diverticulosis compared with controls. In the muscularis propria, the amount of total soluble collagen also was higher in both uncomplicated and complicated diverticulosis samples than in the controls. Tissue inhibitor of metalloproteinase-1 and metalloproteinase-2 mRNA was significantly increased in diverticulosis compared with controls. Macrophage-like and fibroblast-like cells stained strongly positive for tissue inhibitor of metalloproteinases in the submucosa, serosa, and muscularis propria and in areas around the blood vessels. CONCLUSIONS: Colonic diverticulosis is associated with altered collagen content and tissue inhibitor of metalloproteinases expression. These factors may play a role in remodeling the gut wall in this condition.
AB - PURPOSE: Thickening of the muscularis propria is a key pathologic feature of colonic diverticulosis but its cause is unknown. This study was designed to investigate the role of collagens, matrix metalloproteinases, and tissue inhibitor of metalloproteinases in colonic diverticulosis. METHODS: Collagen content was determined by Sircol Collagen Assay and standard van Gieson staining. Messenger-RNA expression for matrix metalloproteinases and tissue inhibitor of metalloproteinase was analyzed by quantitative competitive reverse transcription polymerase chain reaction. Immunohistochemical staining was performed to localize tissue inhibitor of metalloproteinases in sections. RESULTS: In mucosa and submucosal layer, complicated diverticular disease samples had a higher collagen content than uncomplicated disease, which in turn had higher levels than controls. There was an 18-fold increase in tissue inhibitor of metalloproteinase-1 mRNA, and a threefold increase in tissue inhibitor of metalloproteinase-2 mRNA in complicated diverticulosis compared with controls. In the muscularis propria, the amount of total soluble collagen also was higher in both uncomplicated and complicated diverticulosis samples than in the controls. Tissue inhibitor of metalloproteinase-1 and metalloproteinase-2 mRNA was significantly increased in diverticulosis compared with controls. Macrophage-like and fibroblast-like cells stained strongly positive for tissue inhibitor of metalloproteinases in the submucosa, serosa, and muscularis propria and in areas around the blood vessels. CONCLUSIONS: Colonic diverticulosis is associated with altered collagen content and tissue inhibitor of metalloproteinases expression. These factors may play a role in remodeling the gut wall in this condition.
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U2 - 10.1007/s10350-003-0050-5
DO - 10.1007/s10350-003-0050-5
M3 - Article
C2 - 14991500
AN - SCOPUS:10744229407
SN - 0012-3706
VL - 47
SP - 371
EP - 379
JO - Diseases of the colon and rectum
JF - Diseases of the colon and rectum
IS - 3
ER -