Up-regulation of collagen and tissue inhibitors of matrix metalloproteinase in colonic diverticular disease.
OBJECTIVE
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.
Department of Surgery, University of Teikyo, Tokyo, Japan.
Toshiki
T
Mimura
Adrian C
AC
Bateman
Ronald L
RL
Lee
Penelope A
PA
Johnson
Peter J
PJ
McDonald
Ian C
IC
Talbot
Michael A
MA
Kamm
Thomas T
TT
MacDonald
Sylvia L F
SL
Pender
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D043963:Diverticulosis, Colonic / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases