Use of tight junction binders to analyze the barrier function of human placental JEG-3 cells.

INTRODUCTION: The human placental trophoblast layer is a crucial barrier to the transfer of xenobiotics from maternal to fetal fluids. Intercellular spaces between adjacent trophoblast cells are sealed by bicellular and tricellular tight junctions (TJs), which respectively include claudins and angulins. However, which TJ components are involved in the barrier function of placental trophoblast cells remains unclear. METHODS: In this study, we used proteins that bind to the extracellular domain of claudins or angulins (hereafter referred to as binders) to investigate the contributions of various TJ components to barrier function in JEG-3 cells, a human trophoblast model. RESULTS: In this system, claudin binders enhanced the permeation of paracellular passage markers (dextrans with molecular mass of ≤150 kDa) and thus more effectively attenuated TJ integrity than did angulin binders. Gene expression analysis revealed that claudin-4 and angulin-1 are key components in bicellular and tricellular TJs, respectively. CONCLUSIONS: This study is the first to characterize the barrier function of TJ components in JEG-3 cell monolayers, a human trophoblast model.