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Fibrogenesis and fibrolysis in collagenous colitis. Patterns of procollagen types I and IV, matrix-metalloproteinase-1 and -13, and TIMP-1 gene expression.
- Source :
-
The American journal of pathology [Am J Pathol] 1999 Aug; Vol. 155 (2), pp. 493-503. - Publication Year :
- 1999
-
Abstract
- 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 alpha1(I) and alpha1(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 alpha-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 alpha1(I), procollagen alpha1(IV), and TIMP-1 transcript levels were found in alpha-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 alpha1(I)- and alpha1(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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Collagenases genetics
Diarrhea metabolism
Diarrhea pathology
Epithelium anatomy & histology
Epithelium pathology
Female
Gene Expression
Humans
In Situ Hybridization
Male
Matrix Metalloproteinase 1
Matrix Metalloproteinase 13
Middle Aged
Mucous Membrane anatomy & histology
Mucous Membrane pathology
Procollagen analysis
Tenascin analysis
Tenascin metabolism
Colitis metabolism
Colitis pathology
Collagen metabolism
Collagenases metabolism
Procollagen metabolism
Tissue Inhibitor of Metalloproteinase-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9440
- Volume :
- 155
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 10433942
- Full Text :
- https://doi.org/10.1016/S0002-9440(10)65145-0