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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Clin+Chim+Acta 2019 ; 489 (ä): 203-211 Nephropedia Template TP
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Hypoxia-induced and HIF1alpha-VEGF-mediated tight junction dysfunction in choriocarcinoma cells: Implications for preeclampsia #MMPMID29223764
Zhang Y; Zhao HJ; Xia XR; Diao FY; Ma X; Wang J; Gao L; Liu J; Gao C; Cui YG; Liu JY
Clin Chim Acta 2019[Feb]; 489 (ä): 203-211 PMID29223764show ga
INTRODUCTION: Accumulated data indicate that placental hypoxia is implicated in the pathogenesis of preeclampsia (PE). Tight junction (TJ) is important structure that sustains normal placental barrier function, its dysregulation under hypoxia has been observed. This study was designed to explore hypoxia-induced TJ dysfunction in trophoblast cells and its possible involvement in PE pathophysiology. METHODS: Choriocarcinoma cells were grown in a monolayer and treated with cobalt chloride (CoCl(2)) to induce hypoxia. TJ architecture was assessed using transmission electron microscopy, and locations of TJ proteins were determined by immunofluorescence. TJ functions were assessed by transepithelial electrical resistance (TER) and increased cell paracellular permeability (CPP), and the expression of TJ-related proteins, HIF-1alpha and VEGF was measured. RESULTS: The TJ functions of trophoblast cells were significantly altered by hypoxia; TER decreased and CPP increased in a time- and concentration-dependent manner. Significant alterations in TJ protein expression and increases in HIF1alpha and VEGF expression were observed in hypoxic cells, and these effects were attenuated by pretreatment with YC-1. Moreover, corresponding changes in TJ protein expression were also detected in preeclamptic placentas. CONCLUSION: These data demonstrate that trophoblast cells undergo significant changes in TJ protein expression under hypoxic conditions and highlight the potential significance of the HIF1alpha-VEGF axis in the regulation of TJ structure and function in the preeclamptic placenta.