Proliferative effects of excretory/secretory products from Clonorchis sinensis on the human epithelial cell line HEK293 via regulation of the transcription factor E2F1.

Clonorchis sinensis is one of the most prevalent parasitic helminths of humans in East Asia. Although several complications in bile duct epithelial cells are caused by C. sinensis infection, the mechanism is not clearly understood. To clarify the effects of C. sinensis excretory-secretory products (ES products) on bile duct epithelial cells, we investigated their effects on the human embryonic kidney epithelial cell line HEK293 in vitro. Our results show that ES products alter the proportion of cells in each stage of the cell cycle and induce HEK293 cell proliferation. Among cell cycle-related proteins, the expression of cyclin E increased markedly after treatment with ES products, indicating that the G1/S transition occurred. In addition, the expression of the transcription factor E2F1 was up-regulated by the addition of ES products. Small interfering RNA (siRNA) was used to demonstrate that the transcription factor E2F1 is a key factor in the control of cell proliferation in HEK293 cells. The present results demonstrate that ES products from C. sinensis stimulate cell proliferation by inducing E2F1 expression. We suggest that the ES products released from C. sinensis during infection may play an important role in the development of cholangiocarcinoma via the overgrowth of the bile duct epithelium.