Matrix metallopeptidase expression and modulation by transforming growth factor-β1 in equine endometrosis.
Abstract: Equine endometrial fibrosis (endometrosis) is described as a degenerative chronic condition in the uterus. Its characteristic feature is excessive deposition of extracellular matrix (ECM) components around the endometrial glands and stroma. Although matrix metallopeptidases (MMPs) that mediate ECM turnover are important factors in the process of fibrosis, knowledge of their expression and regulation in endometrosis is limited. In other species, one of the important regulators of MMPs and tissue inhibitors of MMPs (TIMPs) is transforming growth factor (TGF)-β1. The goal of this study was to determine (i) endometrial expression of MMPs and TIMPs during endometrosis and (ii) the effect of TGF-β1 on expression of MMPs and TIMPs in equine endometrial fibroblasts and epithelial cells. In the follicular phase of the estrous cycle, MMP-1, -2, -9, and TIMP concentrations were higher during endometrosis than in healthy endometrium (P < 0.05). In the midluteal phase, MMP-3 concentration was lower in severe endometrosis compared to healthy endometrium (P < 0.05). In fibroblasts, TGF-β1 upregulated MMP-1, -9, -13, and TIMP1, but downregulated MMP-3 secretion (P < 0.05). In epithelial cells, TGF-β1 upregulated MMP-1, -9, -13, and TIMP secretion (P < 0.05). Endometrial expression of MMPs and TIMPs is altered during endometrosis. TGF-β1 is a regulator of endometrial ECM remodeling via its effect on MMPs and TIMPs in equine endometrial fibroblasts and epithelial cells.
Publication Date: 2020-01-24 PubMed ID: 31980722PubMed Central: PMC6981191DOI: 10.1038/s41598-020-58109-0Google Scholar: Lookup
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- Journal Article
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Summary
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This research article investigates the role of matrix metallopeptidases (MMPs) and their regulator, transforming growth factor (TGF)-β1, in equine endometrosis, a degenerative condition in horse uteruses characterized by abnormal tissue growth.
Understanding Equine Endometrosis
- The study focuses on equine endometrosis, a chronic degenerative condition impacting horses’ uteruses, characterized by excessive growth of the extracellular matrix (ECM) components enveloping endometrial glands and stroma.
- Changes in the secretion and expression of matrix metallopeptidases (MMPs), enzymes critical for managing ECM component turnover, have been identified as significant factors in the progression of fibrosis, the accumulation of fibrous connective tissue that characterizes endometrosis.
Investigating the Role of MMPs and TGF-β1
- The researchers aimed to study the endometrial expression of MMPs and tissue inhibitors of MMPs (TIMPs) during endometrosis, and how TGF-β1 influences their expression in endometrial fibroblasts and epithelial cells.
- In other species, TGF-β1 has been identified as a significant regulator of MMPs and TIMPs, suggesting a potential determinant factor in equine endometrosis as well.
Findings from the Research
- During the follicular phase of the estrous cycle, concentrations of several types of MMPs (-1, -2, -9) and TIMPs were found to be higher in horses suffering from endometrosis, compared to those with healthy endometrium.
- On the other hand, during the midluteal phase, MMP-3 concentration was observed to be lower in severe endometrosis cases compared to healthy uteruses.
- The study also discovered that in fibroblasts, TGF-β1 upregulated certain MMPs (-1, -9, -13) and TIMP1, but downregulated the secretion of MMP-3.
- In epithelial cells, TGF-β1 upregulated the secretion of similar MMPs (-1, -9, -13), as well as TIMPs.
- The findings indicate a shift in endometrial expression of MMPs and TIMPs during endometrosis, shedding light on TGF-β1’s crucial role in regulating ECM remodeling via its effect on these enzymes and inhibitors.
Cite This Article
APA
Szóstek-Mioduchowska A, Słowińska M, Pacewicz J, Skarzynski DJ, Okuda K.
(2020).
Matrix metallopeptidase expression and modulation by transforming growth factor-β1 in equine endometrosis.
Sci Rep, 10(1), 1119.
https://doi.org/10.1038/s41598-020-58109-0 Publication
Researcher Affiliations
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland. a.szostek-mioduchowska@pan.olsztyn.pl.
- Department of Gamete and Embryo Biology,Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland.
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland.
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland.
- Laboratory of Reproductive Physiology Graduate School of Natural Science and Technology, Okayama University, 700-8530, Okayama, Japan.
- Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.
MeSH Terms
- Animals
- Cells, Cultured
- Endometriosis / enzymology
- Endometriosis / physiopathology
- Endometriosis / veterinary
- Endometrium / metabolism
- Endometrium / pathology
- Epithelial Cells / drug effects
- Epithelial Cells / metabolism
- Estrous Cycle
- Female
- Fibroblasts / drug effects
- Fibroblasts / metabolism
- Fibrosis
- Gene Expression Regulation, Enzymologic / drug effects
- Horse Diseases / enzymology
- Horse Diseases / physiopathology
- Horses
- Matrix Metalloproteinases / biosynthesis
- Matrix Metalloproteinases / genetics
- RNA, Messenger / biosynthesis
- RNA, Messenger / genetics
- Tissue Inhibitor of Metalloproteinases / biosynthesis
- Tissue Inhibitor of Metalloproteinases / genetics
- Transforming Growth Factor beta1 / pharmacology
- Transforming Growth Factor beta1 / physiology
Conflict of Interest Statement
The authors declare no competing interests.
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