Advanced glycation end products increased placental vascular permeability of human BeWo cells via RAGE/NF-kB signaling pathway

Abstract

Objective: This study aimed to investigate the mechanisms of advanced glycation end products (AGEs) on cell tight conjunction and placental vascular permeability in BeWo cells.

Study design: Monolayer permeability assay and transmission electron microscopy were employed to reveal the transformation of the placental vascular permeability and cell tight conjunction. Immunofluorescence, western blot and RT-qPCR were adopted to determine the protein and mRNA levels. Anti-RAGE and NF-kB inhibitor (PDTC) were used to inactivate the RAGE/NF-kB signaling pathway.

Results: AGEs significantly decreased trans-epithelial electrical resistance (TEER), while increased paracellular permeability (P < 0.05). TEM showed that AGEs made cell junction loose. AGEs inhibited ZO-1 and Occludin expressions, while anti-RAGE or PDTC partially restored their levels. AGEs also significantly increased mRNA RAGE and NF-kB expressions in BeWo cells (P < 0.05), and their expressions were inhibited by anti-RAGEy or PDTC.

Conclusion: AGEs could reduce the expressions of ZO-1 and Occludin by activating RAGE/NF-kB signaling pathway, thus increasing placental vascular permeability.

Keywords: Advanced glycation end products; Human BeWo cells; RAGE/NF-kB pathway; Tight junctions.