Inflammation location, but not type, determines the increase in TGF-beta1 and IGF-1 expression and collagen deposition in IBD intestine.
OBJECTIVE
Inflammatory bowel disease (IBD) is frequently complicated by extracellular matrix (ECM) changes that may result in fibrosis. Transforming growth factor (TGF)-beta1 and insulin-like growth factor (IGF)-1 mediate numerous ECM changes. Our aim was to determine whether TGF-beta1 and IGF-1 are involved in intestinal ECM collagen regulation and what impact the inflammatory infiltrate has on their expression.


METHODS
TGF-beta1 and IGF-1 mRNA and protein were assessed in fibrosed Crohn's disease (CD), inflamed CD, inflamed ulcerative colitis (UC), and control intestine using in situ hybridization and immunohistochemistry. Collagen types I and III were quantified by electron immunohistochemistry.


RESULTS
In CD, increased TGF-beta1 and IGF-1 mRNA expression was transmural. In UC, the increase was confined to the lamina propria and submucosa. In both, distribution of TGF-beta1 and IGF-1 protein matched mRNA expression and coincided with the distribution of the inflammatory infiltrate. An increase in the collagen type III:I ratio in both CD and UC also coincided with the inflammatory infiltrate.


CONCLUSIONS
These findings suggest that TGF-beta1 and IGF-1 are involved in intestinal ECM remodeling in IBD, and their enhanced expression depends on the presence and location of inflammatory infiltrates rather than the type of IBD.
Lawrance
I C
IC
Division of Molecular Medicine, John Curtin School of Medical Research, Australian National University, Australian Capital Territory. ian.c.lawrance@health.wa.gov.au
Maxwell
L
L
Doe
W
W
D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I; D003094:Collagen