The activation of P2Y11 inhibits cell proliferation by induction of cell cycle arrest and cell autophagy in endothelial cells

Extracellular ATP mediates a range of physiological effects, including cell proliferation, maturation and migration. However, the effect of ATP on cell proliferation has been contradictory, and the mechanism is not fully understood. In this study, we found that extracellular ATP inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs). Treatment with ATP did not induce apoptosis but induced cell cycle arrest in S phase. ERK inhibitor U0126 reversed the inhibition of cell proliferation, suggesting the involvement of ERK signaling. The endothelial cells expressed P2Y11 and suramin blocked ATP‐induced inhibition of cell proliferation, suggesting that P2Y11 was contributed to the inhibition. This assumption was supported by the observation that knockdown of P2Y11 by RNA interference reversed the inhibition of cell proliferation and ameliorated cell cycle arrest in S phase. ATP promoted endothelial cell autophagy which was also blocked by P2Y11 down‐regulation. Taken together, these results suggested that ATP inhibited cell proliferation by triggering signaling to induce cell cycle arrest and cell autophagy via P2Y11 in endothelial cells.