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(American Journal of Pathology. 1999;155:493-503.)
© 1999 American Society for Investigative Pathology

Regular Articles

Fibrogenesis and Fibrolysis in Collagenous Colitis

Patterns of Procollagen Types I and IV,Matrix-Metalloproteinase-1 and -13, and TIMP-1 Gene Expression

Ute Günther^*, Detlef Schuppan, Michael Bauer, Harald Matthes^*, Andreas Stallmach^§, Annette Schmitt-Gräff^¶, Ernst-Otto Riecken^* and Hermann Herbst^||

From the Department of Gastroenterology^*
and Institute of Pathology,
University Hospital Benjamin Franklin, Free University; Berlin; the Department of Gastroenterology,
University of Erlangen, Erlangen; the Department of Internal Medicine II,^§
University Hospital, Homburg/Saar; the Institute of Pathology,^¶
University of Freiburg im Breisgau; and the Institute of Pathology,^||
University Hospital Eppendorf, Hamburg, Germany

Collagenous colitis is characterized by the deposition of a superficial subepithelial collagenous layer, the pathogenesis of which is unknown. Because the excess matrix deposition is potentially reversible, a labile imbalance between fibrogenesis and fibrolysis may be suspected. Expression of procollagen 1(I) and 1(IV), matrix-metalloproteinase (MMP)-1 and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 genes was semiquantitated by in situ hybridization on serial biopsies of 12 patients with collagenous colitis and compared to controls. Collagen types I, III, IV, and VI, tenascin, undulin/collagen XIV, and -actin were localized by immunohistology. The superficial collagen layer stained strongly for collagen types I, III, and VI, and particularly for tenascin, but not for undulin. Elevated procollagen 1(I), procollagen 1(IV), and TIMP-1 transcript levels were found in -actin-positive cells with linear distribution underneath the superficial collagenous layer, whereas MMP-1 RNA expression was variable and restricted to cell clusters. MMP-13 expression was undetectable. The patterns of procollagen 1(I)- and 1(IV)-specific labeling, combined with an intense tenascin- but absent undulin-specific staining, indicate deposition of an immature interstitial matrix that may be susceptible to degradation. The restricted MMP-1 RNA expression, counteracted by increased TIMP-1 expression, suggests locally impaired fibrolysis as a relevant factor in the pathogenesis of collagenous colitis.

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