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Theriogenology2020; 153; 74-84; doi: 10.1016/j.theriogenology.2020.04.040

Prostaglandins effect on matrix metallopeptidases and collagen in mare endometrial fibroblasts.

Abstract: An increasing number of studies have shown that prostaglandins (PGs) exert multiple regulatory actions in the processes associated to tissue remodeling and fibrosis. Extracellular matrix (ECM) turnover is mediated by matrix metallopeptidases (MMPs). The knowledge about the regulation of their expression in mare endometrium is still limited. Thus, the aim of this study was to investigate whether: (i) profibrotic transforming growth factor (TGF)-β1 modulates PG production in equine endometrium; and (ii) PGE and PGF modulate MMPs, their tissue inhibitors (TIMPs), and collagen 1 (COL1) expression. In experiment 1, the effect of TGF-β1 (5 ng/mL) on PG secretion and PG synthases mRNA transcription, after 24 and 48 h treatment of mare endometrial fibroblast and epithelial cells was investigated using ELISA and qPCR. In experiment 2, the effects of PGE and PGF in doses 10M and 10M on secretion and MMP1, 2, 9, 13, TIMP1, 2, and COL1A1 mRNA transcription in mare endometrial fibroblasts were assessed. Transforming growth factor-β1 treatment decreased secretion of PGF by endometrial fibroblasts (P < 0.05) and PGF and PGE by endometrial epithelial cells (P < 0.05). Prostaglandin E increased MMP-2 and MMP-9, and decreased MMP-13 secretion by endometrial fibroblasts (P < 0.05). Additionally, PGF treatment increased MMP-2, MMP-13 and COL1, but decreased MMP-1 secretion by endometrial fibroblasts (P < 0.05). Prostaglandins may be involved in the processes associated to pathological endometrial remodeling by their effect on MMP expression. The effect of PGF on COL1 secretion from fibroblasts suggests its profibrotic role in pathological endometrial remodeling.
Publication Date: 2020-05-11 PubMed ID: 32442743DOI: 10.1016/j.theriogenology.2020.04.040Google Scholar: Lookup
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  • Journal Article

Summary

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The research examines how prostaglandins (PGs), substances in the body that control processes such as inflammation and blood flow, may affect tissue remodeling in the endometrium of horses. By focusing on PGs’ influence on matrix metallopeptidases (MMPs) and collagen, the study uncovers potential pathways of pathological endometrial remodeling that may underlie certain reproductive disorders.

Research Purpose and Methods

  • The study aimed to delve into two primary questions: whether the profibrotic transforming growth factor (TGF)-β1 influences PG production in equine endometrium, and whether PGE and PGF affect the expression of MMPs, their tissue inhibitors (TIMPs), and collagen 1 (Col1). This research is integral to understanding how PGs might regulate endometrial tissue remodeling.
  • The researchers conducted two experiments using ELISA and qPCR method for measuring the effect of TGF-β1 on PG secretion and changes in mRNA transcription of PG synthases in mare endometrial fibroblast and epithelial cells. They further investigated the influence of PGE and PGF on the secretion of MMP1, 2, 9, 13, TIMP1, 2, and COL1A1 mRNA transcription in mare endometrial fibroblasts.

Key Findings

  • It was found that treatment with TGF-β1 reduced the secretion of PGF by endometrial fibroblasts as well as PGF and PGE by endometrial epithelial cells.
  • Exposure to Prostaglandin E increased MMP-2 and MMP-9 secretion, and reduced MMP-13 secretion in endometrial fibroblasts.
  • Prostaglandin F treatment increased the secretion of MMP-2, MMP-13, and COL1, but decreased the secretion of MMP-1 by endometrial fibroblasts.

Implications and Interpretation

  • The research suggests that PGs could have a significant role in pathological endometrial remodeling due to their impact on MMPs, which play a critical role in the degradation of extracellular matrix components, important for tissue repair and remodeling.
  • Furthermore, the influence of PGF on COL1 secretion from fibroblasts may suggest a profibrotic role in pathological endometrial remodeling. Fibrosis refers to the development of excessive connective tissue as a repair response, leading to a stiffening or scarring affect that could lead to dysfunction in horse reproduction.

Cite This Article

APA
Szóstek-Mioduchowska AZ, Baclawska A, Rebordão MR, Ferreira-Dias G, Skarzynski DJ. (2020). Prostaglandins effect on matrix metallopeptidases and collagen in mare endometrial fibroblasts. Theriogenology, 153, 74-84. https://doi.org/10.1016/j.theriogenology.2020.04.040

Publication

ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 153
Pages: 74-84
PII: S0093-691X(20)30275-2

Researcher Affiliations

Szóstek-Mioduchowska, Anna Zuzanna
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima Str 10, 10-748, Olsztyn, Poland. Electronic address: a.szostek-mioduchowska@pan.olsztyn.pl.
Baclawska, Agnieszka
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima Str 10, 10-748, Olsztyn, Poland.
Rebordão, Maria Rosa
  • CIISA - Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Department of Animal Sciences, Coimbra College of Agriculture, Polytechnic Institute of Coimbra, Coimbra, Portugal.
Ferreira-Dias, Graca
  • CIISA - Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
Skarzynski, Dariusz Jan
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima Str 10, 10-748, Olsztyn, Poland.

MeSH Terms

  • Animals
  • Collagen / genetics
  • Collagen / metabolism
  • Dinoprostone / pharmacology
  • Endometrium / cytology
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression Regulation / drug effects
  • Horses
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism
  • Metalloproteases / genetics
  • Metalloproteases / metabolism
  • Prostaglandins / pharmacology
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Tissue Inhibitor of Metalloproteinases / metabolism
  • Transforming Growth Factor beta1 / pharmacology

Conflict of Interest Statement

Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper.

Citations

This article has been cited 8 times.
  1. Pandur E, Pap R, Jánosa G, Horváth A, Sipos K. Fractalkine Improves the Expression of Endometrium Receptivity-Related Genes and Proteins at Desferrioxamine-Induced Iron Deficiency in HEC-1A Cells.. Int J Mol Sci 2023 Apr 27;24(9).
    doi: 10.3390/ijms24097924pubmed: 37175630google scholar: lookup
  2. Katila T, Ferreira-Dias G. Evolution of the Concepts of Endometrosis, Post Breeding Endometritis, and Susceptibility of Mares.. Animals (Basel) 2022 Mar 19;12(6).
    doi: 10.3390/ani12060779pubmed: 35327176google scholar: lookup
  3. Amaral A, Fernandes C, Szóstek-Mioduchowska A, Lukasik K, Rebordão MR, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G. The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium.. Life (Basel) 2021 Oct 19;11(10).
    doi: 10.3390/life11101107pubmed: 34685478google scholar: lookup
  4. Rebordão MR, Amaral A, Fernandes C, Silva E, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G. Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF(2α) Pathway in the Mare Endometrium.. Animals (Basel) 2021 Sep 6;11(9).
    doi: 10.3390/ani11092615pubmed: 34573581google scholar: lookup
  5. Amaral A, Fernandes C, Szóstek-Mioduchowska A, Rebordão MR, Skarzynski DJ, Ferreira-Dias G. Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium.. Int J Mol Sci 2021 May 19;22(10).
    doi: 10.3390/ijms22105333pubmed: 34069423google scholar: lookup
  6. 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).
    doi: 10.3390/ani11010208pubmed: 33467081google scholar: lookup
  7. 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.
    doi: 10.3389/fvets.2020.582211pubmed: 33195599google scholar: lookup
  8. Szóstek-Mioduchowska A, Leciejewska N, Zelmańska B, Staszkiewicz-Chodor J, Ferreira-Dias G, Skarzynski D. Lysophosphatidic acid as a regulator of endometrial connective tissue growth factor and prostaglandin secretion during estrous cycle and endometrosis in the mare.. BMC Vet Res 2020 Sep 17;16(1):343.
    doi: 10.1186/s12917-020-02562-6pubmed: 32943074google scholar: lookup