Gene Expression of MMP-1, MMP-2 and TNF-α in the Endometrium of Mares With Different Degrees of Fibrosis

Centeno, L. A. M.; Bastos, H.B.A.; Bueno, Valquíria; Trentin, J. M.; Fiorenza, Maryse; Rechsteiner, Sandra Mara da Encarnação Fiala; Filho, Nélson Alexandre Kretzmann; Mattos, Rodrigo Costa; Rubin, MA

doi:10.1016/j.jevs.2018.05.182

Cited by 6 publications

(8 citation statements)

References 6 publications

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“…In their study, Centeno et al [31] found any differences in TNFA expression in endometrial tissue of mares with different degree of fibrosis; the expression of TNFA in our study was greater in G1 mares than older ones. It is possible that the stage of the estrous cycle at the moment of the uterine biopsy influenced the TNFA expression in specimens: in fact, Centeno et al [31] used tissues deriving from mare in diestrus (D 5 – D 10 ), while in the present study, biopsies were performed during oestrus.…”

Section: Discussioncontrasting

confidence: 56%

“…The cytokine TNFA is considered to be indicative of acute inflammatory process but it is also involved in the regulation of equine estrus cycle [31, 32]. In their study, Centeno et al [31] found any differences in TNFA expression in endometrial tissue of mares with different degree of fibrosis; the expression of TNFA in our study was greater in G1 mares than older ones.…”

Section: Discussioncontrasting

confidence: 43%

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Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season

et al. 2019

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BackgroundDespite being one of the major causes of infertility in mares, the mechanisms responsible for equine endometrosis are still unclear and controversial. In the last few years, many investigations focused on local immune response modulation. Since it is generally accepted that endometrial fibrosis increases with age, we hypothesize that older mares could show altered local immune modulation, initiating a pro-inflammatory and tissue remodeling cascade of events that could lead to endometrosis. The aim of this study, indeed, is to evaluate and describe the local gene expression of genes involved in acute inflammatory response and fibrosis (COL1A1, COL3A1, TNFA, MMP9, IL6, TGFB1 and TGFBR1), together with others associated to immune modulation (DEFB4B, IDO1 and FOXP3), in uterine specimens from mares of different age.ResultsTwenty-five Standardbred mares were involved in the study with age ranging from 7 to 19 years (mean 10.40 ± 4.42). They were divided by age into two groups: G1 (n = 15, less than 10 years old) and G2 (N = 10, greater than 11 years old). Specimens from the uterus’ right horn-body junction were collected and processed for histology evaluation and RT-qPCR assay.Gene expression of DEFB4B, MMP9 and TNFA was higher in younger mares, suggesting a balance in immune modulation and tissue remodeling. Interleukin-6 and COL3A1 gene expressions were greater in older animals, probably indicating inflammatory pathways activation and fibrosis increase. Although no differences in fibrosis and inflammation distribution could be found with histological examination among G1 and G2, our results suggest a possible involvement of DEF4BB in regulating the local immune response in younger mare’s uterus (G1); age may contribute to the dis-regulation of DEFB4B transcription and, indirectly, influence the extracellular matrix homeostasis. Transcription of IDO1 and FOXP3 genes, instead, does not seem to be age related, or to be involved in local immune-response and tissue remodeling functions.ConclusionsFurther investigations are needed in order to clarify the interactions between the expression of DEFB4B, IL6, TNFA, COL3A1 and MMP9 and other local signals of immune-modulation and tissue remodeling, in mares in a prospective study design.

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Section: Discussioncontrasting

confidence: 56%

Section: Discussioncontrasting

confidence: 43%

Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season

et al. 2019

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“…In turn, Aresu et al 9 used immunohistochemistry to demonstrate that there were no differences in expression of MMP-2 and MMP-9 between healthy endometrium and endometrium effected by fibrosis in mares. Additionally, Centeno et al 21 showed that transcription of Mmp1 mRNA was downregulated and transcription of Mmp2 was upregulated during severe mare endometrial fibrosis. Our studies are in agreement with those of Walter et al 8 and partially with those of Centeno et al 21 .…”

Section: Discussionmentioning

confidence: 99%

Matrix metallopeptidase expression and modulation by transforming growth factor-β1 in equine endometrosis

Szóstek‐Mioduchowska

Słowińska

Pacewicz

et al. 2020

Sci Rep

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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.

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“…Comparing the normal and fibrotic equine endometrium, Aresu et al [ 34 ] found no alteration in MMP-2/-9 expression. However, MMP-2 transcription [ 35 ] and its active form [ 36 ] were up-regulated in mare endometrosis. Our latest in vitro studies in equine endometrium revealed that the expression of MMPs is altered by factors involved in inflammation [transforming growth factor (TGF) β1, interleukins and prostaglandins] [ 37 , 38 , 39 ], and could contribute to the fibrotic response to elastase [ 20 ] and cathepsin G [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions

Amaral

Fernandes

Rebordão

et al. 2021

Animals

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Neutrophils can originate neutrophil extracellular traps (NETs). Myeloperoxidase (MPO) is a peroxidase found in NETs associated to equine endometrosis and can be inhibited by 4-aminobenzoic acid hydrazide (ABAH). Metallopeptidases (MMPs) participate in extracellular matrix stability and fibrosis development. The objectives of this in vitro work were to investigate, in explants of mare’s endometrium, (i) the ABAH capacity to inhibit MPO-induced collagen type I (COL1) expression; and (ii) the action of MPO and ABAH on the expression and gelatinolytic activity of MMP-2/-9. Explants retrieved from the endometrium of mares in follicular or mid-luteal phases were treated with MPO, ABAH, or their combination, for 24 or 48 h. The qPCR analysis measured the transcription of COL1A2, MMP2, and MMP9. Western blot and zymography were performed to evaluate COL1 protein relative abundance and gelatinolytic activity of MMP-2/-9, respectively. Myeloperoxidase elevated COL1 relative protein abundance at both treatment times in follicular phase (p < 0.05). The capacity of ABAH to inhibit MPO-induced COL1 was detected in follicular phase at 48 h (p < 0.05). The gelatinolytic activity of activated MMP-2 augmented in mid-luteal phase at 24 h after MPO treatment, but it was reduced with MPO+ABAH treatment. The activity of MMP-9 active form augmented in MPO-treated explants. However, this effect was inhibited by ABAH in the follicular phase at 48 h (p < 0.05). By inhibiting the pro-fibrotic effects of MPO, it might be possible to reduce the development of endometrosis. Metallopeptidase-2 might be involved in an acute response to MPO in the mid-luteal phase, while MMP-9 might be implicated in a prolonged exposition to MPO in the follicular phase.

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Gene Expression of MMP-1, MMP-2 and TNF-α in the Endometrium of Mares With Different Degrees of Fibrosis

Cited by 6 publications

References 6 publications

Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season

Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season

Matrix metallopeptidase expression and modulation by transforming growth factor-β1 in equine endometrosis

Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions

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