Original article - Macrophage migration inhibitory factor is involved in endovascular trophoblast cell function in vitro

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Aleksandra Vilotic
Milica Jovanovic Krivokuca
Ivana Stefanoska
Svetlana Vrzic Petronijevic
Milos Petronijevic
Ljiljana Vicovac

Abstract

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine abundantly present at the feto-maternal interface proposed to play a role in establishment of pregnancy. We have previously shown that pharmacological inhibition of enzymatic activity of MIF decreases extravillous trophoblast invasion and migration in vitro. This study aimed to further elucidate potential role of endogenous trophoblast MIF, and to assess its importance for endovascular trophoblast cell function in particular. Attenuation of MIF by siRNA reduced HTR-8/SVneo cell invasion through Matrigel (59 % of control), expression of integrin α1 (86 % of control) and levels of MMP2 and MMP9 (87 % and 57 % of control, respectively). MIF specific siRNA reduced the ability of HTR-8/SVneo to differentiate in to endothelial-like phenotype, as determined by Matrigel tube formation assay. The total tube length was decreased to 68.6 %, while the number of branching points was reduced to 57.8 % of control. HTR-8/SVneo cell capacity to integrate into HUVEC monolayers was reduced by knock-down of MIF. This could be partly caused by reduced N-cadherin expression to 63 % of control, which decreased with knock-down of MIF, as the expression of this protein was recently shown essential for trophoblast-endothelial interaction. These novel findings indicate a novel role for trophoblast MIF in spiral artery remodeling process.

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How to Cite
Vilotic, A., Jovanovic Krivokuca, M., Stefanoska, I., Vrzic Petronijevic, S., Petronijevic, M., & Vicovac, L. (2019). Original article - Macrophage migration inhibitory factor is involved in endovascular trophoblast cell function in vitro. EXCLI Journal, 18, 1007-1018. https://doi.org/10.17179/excli2019-1630
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