Molecular characterization of soluble factors from human menstrual effluent that induce epithelial to mesenchymal transitions in mesothelial cells |
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Authors: | Email author" target="_blank">Ay?e?Y?DemirEmail author Patrick?G?Groothuis Gerard?A?J?Dunselman Leon?Schurgers Johannes?L?H?Evers Anton?F?P?M?de?Goeij |
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Institution: | (1) Research Institute Growth and Development (GROW), Academic Hospital and Maastricht University, Maastricht, The Netherlands;(2) Department of Obstetrics and Gynaecology, Academic Hospital and Maastricht University, Maastricht, The Netherlands;(3) Department of Biochemistry, Academic Hospital and Maastricht University, Maastricht, The Netherlands;(4) Department of Pathology, Academic Hospital and Maastricht University, Maastricht, The Netherlands;(5) Department of Clinical Chemistry, University Medical Center Utrecht, G03.550, P.O. Box 85500, 3508 GA Utrecht, The Netherlands |
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Abstract: | We have studied menstrual effluent in order to identify soluble menstrual factors that induce epithelial to mesenchymal transitions
(EMT) in mesothelial cells. A variety of molecules, such as nitric oxide and its reaction products, proteases (i.e. matrix
metalloproteinases, plasmin) and proteins and/or peptides (i.e. growth factors: b-fibroblast growth factor, epidermal growth
factor, hepatocyte growth factor, transforming growth factor-β; cytokines: interleukin 1β, tumour necrosis factor-α TNF-α])
may be involved in this process. We have demonstrated that TNF-α is involved in EMT, whereas the other molecules are not.
Biochemical analysis has shown that the inducing menstrual factors are heat-labile molecules, are uncharged at neutral pH,
have a molecular weight between 50–70 kDa (or are bound in complexes of that size) and are eluted in the albumin fraction
during gel filtration chromatography. Further analysis of this fraction by using proteomics and mass spectrometry has led
to the identification of α-enolase and haemoglobin whose inhibition partially prevents EMT. When antibodies against TNF-α,
α-enolase and haemoglobin are combined, EMT is almost completely inhibited. Thus, the candidates for soluble menstrual factors
that induce mesothelial EMT are TNF-α, α-enolase and haemoglobin. |
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Keywords: | Retrograde menstruation Endometrium Peritoneum Endometriosis TNF-α α -Enolase Haemoglobin Human |
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