双酚A通过雌激素受体途径对HaCat细胞缝隙连接的影响

Objective: The aim of this study was to investigate the effects and possible mechanisms of BPA on gap junctional intercellular communication (GJIC) of human normal skin cells HaCat. Methods: A modified E-Screen assay was used to evaluate cell proliferation, fluorescence recovery after photobleaching (FRAP) technique was used to evaluate GJIC function and Real-time Fluorescent Quantitative PCR was used to detect mRNA expression levels. Results: BPA increased cell proliferation rates, prolonged fluorescence recovery times, and reduced fluorescence recovery rates at 1.0×10-8-1.0×10-6 mol/L. Estrogen receptor (ER) inhibitor ICI182780 partially blocked the above effects. MAPK/ERK kinase (MEK) 1/2 inhibitor U0126 completely blocked the promoting effects on cell proliferation, but did not rescue the inhibition of GJIC. BPA 1.0×10-7 mol/L downregulated Cx26 mRNA level. ICI182780 and U0126 inhibited this effect. BPA 1.0×10-7 and 1.0×10-6 mol/L combined with U0126 up-regulated extracellular regulated protein kinases (ERK) 1/2 mRNA levels. BPA 1.0×10-7 mol/L combined with ICI182780 had similar but weaker effects. Conclusion: BPA can promote HaCat proliferation through ER-ERK pathway, inhibit HaCat GJIC function through ER pathway, and downregulate Cx26 mRNA level through ER-ERK pathway. Complete inhibition of ERK pathway can stimulate BPA to promote ERK 1/2 mRNA expression, and ER plays an important role in this effect.