Bacterial LPS differentially modulates the expression of Myoferlin in trophoblast cells

Abstract

Myoferlin, one of the members of the Ferlin family is a membrane protein encoded by the MYOF gene and found in cell membranes, nuclear membranes and cytoplasmic vesicles. A high expression ofMyoferlin is observed in skeletal and cardiacmuscles and weak expression in the brain, kidney and placenta. Myoferlin has been found to be necessary for membrane repairing and regulation of VEGF signal transduction. VEGF is not restricted to the vascular system and contributes to wound healing, cell division and proliferation. Successful implantation of the developing embryo in the maternal uterus is associated with Extravillous Trophoblast (EVT) cell proliferation and invasion of the uterine wall. Decreased EVT proliferation and trophoblast cell death has been associatedwith pregnancy complications such as preeclampsia and intrauterine growth restriction thus resulting in inadequate trophoblast invasion.We have hypothesized that there is a correlation between the down-regulation of Myoferlin and the decreased cell proliferation of trophoblast cells upon bacterial infection. In this study, detection and quantification of Myoferlin on JEG-3 cell line wasperformedupon treatmentwith Lipopolysaccharide (LPS). Proteomics quantitative data, revealed that LPS treatment induced a significant (p=0.0002)decrease in theexpression level ofMyoferlin in trophoblast cell line. Myoferlin quantification estimated by flow cytometry also showed significant decrease in LPS treated JEG-3 cells in dose dependent manner. Whereas, fluorescence microscopic imaging results confirmed the same. The cell proliferation assay revealed a significant decrease (62%) in trophoblast cell growth in 48h of LPS treatment. In conclusion, decreased Myoferlin expression is associated with the decreased cell proliferation of trophoblast cells upon bacterial LPS treatment.