The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival

Graham, Amanda; Falcone, Tommaso; Nothnick, Warren B.

doi:10.1093/humrep/dev005

Cited by 48 publications

(60 citation statements)

References 46 publications

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“…Non-neuronal TRPV1 can also be activated by the endocannabinoid anandamide in the rat reproductive system (Cella et al 2008, Scotchie et al 2014. These results are consistent with increased TRPA1 and TRPV1 expression in rat and human endometriosis demonstrated by our laboratory (unpublished results) and literature data (Hucho & Levine 2007, Ilie & Ilie 2013, Graham et al 2015. Increased estrogen synthesis in endometriosis lesions makes those results comparable to these data.…”

Section: Discussionsupporting

confidence: 87%

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

Pohóczky

Kun

Szalontai

et al. 2015

Journal of Molecular Endocrinology

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Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors expressed predominantly in sensory nerves are activated by inflammatory stimuli and mediate inflammation and pain. Although they have been shown in the human endometrium, their regulation and function are unknown. Therefore, we investigated their estrogen-and progesterone-dependent alterations in the rat endometrium in comparison with the estrogenregulated inflammatory cytokine macrophage migration inhibitory factor (MIF). Four-week-old (sexually immature) and four-month-old (sexually mature) female rats were treated with the non-selective estrogen receptor (ER) agonist diethylstilboestrol (DES), progesterone and their combination, or ovariectomized. RT-PCR and immunohistochemistry were performed to determine mRNA and protein expression levels respectively. Channel function was investigated with ratiometric [Ca 2C ] i measurement in cultured primary rat endometrial cells. Both TRP receptors and MIF were detected in the endometrium at mRNA and protein levels, and their localizations were similar. Immunostaining was observed in the immature epithelium, while stromal, glandular and epithelial positivity were observed in adults. Functionally active TRP receptor proteins were shown in endometrial cells by activation-induced calcium influx. In adults, Trpa1 and Trpv1 mRNA levels were significantly up-regulated after DES treatment. TRPA1 increased after every treatment, but TRPV1 remained unchanged following the combined treatment and ovariectomy. In immature rats, DES treatment resulted in increased mRNA expression of both channels and elevated TRPV1 immunopositivity. MIF expression changed in parallel with TRPA1/TRPV1 in most cases. DES up-regulated Trpa1, Trpv1 and Mif mRNA levels in endometrial cell cultures, but 17b-oestradiol having ERa-selective potency increased only the expression of Trpv1. We provide the first evidence for TRPA1/TRPV1 expression and their estrogen-induced up-regulation in the rat endometrium in correlation with the MIF. Journal of Molecular EndocrinologyResearch K POHÓ CZKY and others TRPV1 and TRPA1 in the rat endometrium 56:2 135-149

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Section: Discussionsupporting

confidence: 87%

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

Pohóczky

Kun

Szalontai

et al. 2015

Journal of Molecular Endocrinology

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“…Lastly, overexpression of miR-451 in an immortalized human endometriotic epithelial cell line (12Z) led to the decreased expression of its target YWHAZ which was correlated with decreased cell proliferation. Collectively, both our study 46 and that of Joshi and colleagues 47 demonstrated that miR-451 is capable of modulating cell proliferation and this is associated with alterations in the expression of targets MIF and YWHAZ.…”

Section: Putative Targets Of and Functions For Specific Mirnas In Esupporting

confidence: 62%

“…Our laboratory reported the initial study examining both miR451 expression and function in human tissue and cells. 46 miR-451 is elevated in endometriotic lesion tissue compared with paired eutopic endometrium from women with the disease. 24 miR-451 expression exhibited an inverse association with transcript and protein expression of putative target, macrophage migration inhibitory factor (MIF).…”

Section: Putative Targets Of and Functions For Specific Mirnas In Ementioning

confidence: 94%

MicroRNAs and Endometriosis: Distinguishing Drivers from Passengers in Disease Pathogenesis

Nothnick

2017

Semin Reprod Med

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Endometriosis is a disease common in women of reproductive age, characterized by pelvic pain and infertility. Despite its prevalence, the factors and mechanisms which contribute to the development and survival of ectopic lesions remain uncertain. MicroRNAs (miRNAs) are small RNA molecules that regulate posttranscriptional gene regulation which have been proposed to contribute to the pathogenesis of many diseases including that of endometriosis. This review summarizes the results of initial studies describing differentially expressed miRNAs between endometriotic lesion tissue and eutopic endometrium. Focus then moves toward discussion of studies on examining function of differentially expressed miRNAs to determine if they play a permissive role (driver of the disease) in events conducive to endometriosis progression/survival. Included in this discussion are the potential targets of these miRNAs and how their mis-expression may contribute to the disease. Limitations and challenges faced in studying miRNAs and endometriosis pathogenesis and recommendations to overcome these hurdles are presented at the end.

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“…1C). Regarding miR-451a, Graham's team has recently published two studies showing increased levels of this miRNA in ovarian endometriomas that correlate with lesion size and with its serum levels (30,31). Provided that PF is mainly composed of blood components (32), and usually up-regulated proteins in serum are proportionally up-regulated in PF (33), our results are in accordance with Graham's, suggesting an important role for miR-451a as a mediator of inflammation in the peritoneal microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Micro-RNA profile and proteins in peritoneal fluid from women with endometriosis: their relationship with sterility

Marí-Alexandre¹,

Barceló-Molina²,

Belmonte-López³

et al. 2018

Fertility and Sterility

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The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival

Abstract: This study was funded by the National Institutes of Health/NICHD by grant NIH HD069043 to W.B.N. The authors have no competing interests.

Cited by 48 publications

References 46 publications

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

MicroRNAs and Endometriosis: Distinguishing Drivers from Passengers in Disease Pathogenesis

Micro-RNA profile and proteins in peritoneal fluid from women with endometriosis: their relationship with sterility

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