Autophagy Inhibits Endothelial Progenitor Cells Migration Via the Regulation of MMP2, MMP9 and UPA Under Normoxia Condition

Objective: The aim of this study was to explore the role of autophagy on the regulation of endothelial progenitor cells (EPCs) migration under normoxic condition.

Methods: After EPCs were isolated and characterized in vitro, we employed Atg5 knocking down and rapamycin to monitor the autophagy, and performed wound healing and transwell assay to assess the cell migration. On the mechanism, the expression of matrix metalloproteinases (MMPs) and urokinase type plasminogen activator (uPA) was evaluated.

Results: Atg5 knocking down and rapamycin could respectively inhibit and enhance autophagy, which could result in significantly increased and decreased cell migration in wound healing and transwell assay under normoxic condition. Moreover, Atg5 knocking down could significantly increase the expression of MMP2, MMP9 and uPA in EPCs while rapamycin could decrease the expression of uPA and MMP9. In addition, the mTOR-P70 S6K pathway was also involved in EPCs migration regulation.

Conclusions: These results demonstrated that autophagy could regulate the EPCs migration through mTOR-P70 S6K pathway, and MMP2, MMP9 and uPA may also involve in the regulation mechanism.