Matrix metalloproteinase 2 (MMP-2) and tissue transglutaminase (TG 2) are expressed in periglandular fibrosis in horse mares with endometrosis.
Abstract: Periglandular arrangement of myofibroblasts, associated with the deposition of extracellular matrix (ECM), is a cardinal feature of endometrosis in mares. We hypothesized that a disturbance in the expression of matrix degrading enzymes such as matrix metalloproteinases (MMP's) and matrix cross-linking proteins might lead to an imbalance in deposition and degradation of extracellular matrix components and thereby accentuate degeneration. Therefore, distributions of MMP-2, capable of collagen IV and laminin degradation, and tissue transglutaminase (TG2), a cross-linker of extracellular matrix proteins, were investigated by means of immunohistochemistry on uterine biopsies of healthy mares and animals with endometrosis. It was illustrated that both proteins were present in fibrotic regions of affected endometria, and that they were in most cases colocalized. Periglandular MMP-2 expression was significantly associated with dilated and fibrotic uterine glands. Furthermore, MMP-2 and TG 2 were demonstrated in the stratum compactum of healthy and endometrotic endometria. Gelatin zymography proved that active and inactive pro-form of MMP-2 were present in all examined samples with significantly higher amounts of total and active MMP-2 in affected endometria. TG 2-activity, determined by an in situ assay, was found in cases of severe periglandular fibrosis. We suggest that both enzymes play a major role in changes that occur in ECM homeostasis in endometrial fibrotic regions.
Publication Date: 2005-09-02 PubMed ID: 16136493DOI: 10.14670/HH-20.1105Google Scholar: Lookup
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- Journal Article
Summary
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The research article explores the roles of two enzymes, Matrix Metalloproteinase 2 (MMP-2) and Tissue Transglutaminase (TG 2), in the development of endometrosis, which is a condition of uterine inflammation in horse mares that involves extensive fibrosis and remodeling of the extracellular matrix (ECM).
Researchers’ Hypotheses and Methodology
- The researchers proposed a theory that a disruption in the expression of enzymes that degrade the matrix, such as matrix metalloproteinases (MMPs), and those proteins that cross-link the matrix might lead to an imbalance between ECM components’ deposition and degradation, thus exacerbating degeneration.
- The researchers examined the distributions of two specific enzymes—MMP-2 and tissue transglutaminase (TG2)—in uterine biopsies of healthy mares and animals with endometrosis using a technique known as immunohistochemistry.
- MMP-2 is known to degrade collagen IV and laminin, while TG2 is a cross-linker of ECM proteins.
Findings and Interpretations
- The study showed that both MMP-2 and TG2 were found in fibrotic regions of endometria affected by endometrosis, often co-localizing in the same regions.
- The expression of MMP-2 in periglandular regions was closely associated with dilated and fibrotic uterine glands.
- Both MMP-2 and TG2 were observed in the stratum compactum of both healthy and endometrotic endometria.
- Gelatin zymography, a method used to detect enzymatic activity, showed that both active and inactive forms of MMP-2 were present in all examined samples, with significantly higher amounts of total and active MMP-2 in endometria affected by endometrosis.
- Severe cases of periglandular fibrosis were found to have TG2-activity as determined by an in situ assay technique.
In conclusion, the researchers suggest that due to regulatory changes in the ECM’s homeostasis within fibrotic regions of endometrial tissue, MMP-2 and TG2 could potentially play a critical role in endometrosis pathogenesis.
Cite This Article
APA
Walter I, Handler J, Miller I, Aurich C.
(2005).
Matrix metalloproteinase 2 (MMP-2) and tissue transglutaminase (TG 2) are expressed in periglandular fibrosis in horse mares with endometrosis.
Histol Histopathol, 20(4), 1105-1113.
https://doi.org/10.14670/HH-20.1105 Publication
Researcher Affiliations
- Department of Pathobiology, Institute of Histology and Embryology, University of Veterinary Medicine, Vienna, Austria. Ingrid.Walter@vu-wien.ac.at
MeSH Terms
- Animals
- Electrophoresis, Polyacrylamide Gel
- Endometriosis / enzymology
- Endometriosis / pathology
- Endometrium / enzymology
- Endometrium / pathology
- Female
- Fibrosis
- GTP-Binding Proteins / biosynthesis
- Horses
- Immunoblotting
- Matrix Metalloproteinase 2 / biosynthesis
- Microscopy, Confocal
- Protein Glutamine gamma Glutamyltransferase 2
- Transglutaminases / biosynthesis
Citations
This article has been cited 10 times.- Alpoim-Moreira J, Fernandes C, Pimenta J, Bliebernicht M, Rebordão MR, Castelo-Branco P, Szóstek-Mioduchowska A, Skarzynski DJ, Ferreira-Dias G. Metallopeptidades 2 and 9 genes epigenetically modulate equine endometrial fibrosis. Front Vet Sci 2022;9:970003.
- Jasiński T, Zdrojkowski Ł, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Domino M. Equine Endometrosis Pathological Features: Are They Dependent on NF-κB Signaling Pathway?. Animals (Basel) 2021 Nov 4;11(11).
- Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Pinto-Bravo P, Telo da Gama L, Jan Skarzynski D, Ferreira-Dias G. Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions. Animals (Basel) 2021 Jan 16;11(1).
- Amaral A, Fernandes C, Morazzo S, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Gawronska-Kozak B, Telo da Gama L, Skarzynski DJ, Ferreira-Dias G. The Inhibition of Cathepsin G on Endometrial Explants With Endometrosis in the Mare. Front Vet Sci 2020;7:582211.
- Szóstek-Mioduchowska A, Słowińska M, Pacewicz J, Skarzynski DJ, Okuda K. Matrix metallopeptidase expression and modulation by transforming growth factor-β1 in equine endometrosis. Sci Rep 2020 Jan 24;10(1):1119.
- Marth CD, Firestone SM, Glenton LY, Browning GF, Young ND, Krekeler N. Oestrous cycle-dependent equine uterine immune response to induced infectious endometritis. Vet Res 2016 Nov 8;47(1):110.
- Gebhard C, Fuchs-Baumgartinger A, Razzazi-Fazeli E, Miller I, Walter I. Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma. Can J Vet Res 2016 Jan;80(1):66-73.
- Kendziorski JA, Belcher SM. Strain-specific induction of endometrial periglandular fibrosis in mice exposed during adulthood to the endocrine disrupting chemical bisphenol A. Reprod Toxicol 2015 Dec;58:119-30.
- Falomo ME, Ferroni L, Tocco I, Gardin C, Zavan B. Immunomodulatory Role of Adipose-Derived Stem Cells on Equine Endometriosis. Biomed Res Int 2015;2015:141485.
- Aresu L, Benali S, Giannuzzi D, Mantovani R, Castagnaro M, Falomo ME. The role of inflammation and matrix metalloproteinases in equine endometriosis. J Vet Sci 2012 Jun;13(2):171-7.
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