MCPIP1-induced Autophagy Mediates Ischemia/Reperfusion Injury In Endothelial Cells Via HMGB1 And CaSR

Background/Aims:Monocyte chemotactic protein-1-induced protein 1(MCPIP1)plays a crucial role in ischemia/reperfusion(I/R)injury.Autophagy is involved in activating endothelial cells in response to I/R.However,researchers have not clearly determined whether MCPIP1 mediates I/R injury in endothelial cells via autophagy,and its remains downstream mechanism unclear.In this study,we examined the cascade downstream of I/R-induced MCPIP1 expression that modulates the migration and apoptosis of human umbilical vein endothelial cells(HUVECs)and determined whether autophagy is involved in this process.Methods:1.Protein levels were detected in HUVECs using Western blotting analyses and immunocytochemistry;2.An in vitro scratch assay was used to detect cell migration;3.Cells were transfected with siRNAs to knockdown MCPIP1 and high-mobility group box-1(HMGB1)expression;4.The pharmacological activator of autophagy rapamycin and the specific calcium-sensing receptor(CaSR)inhibitor NPS-2143 were used to confirm the role of autophagy and CaSR in I/R injury.Results:1.I/R induced HMGB1 and CaSR expression in HUVECs;2 Involvement of HMGB1 in I/R-mediated HUVEC migration;3.CaSR specifically participated in I/R-induced HUVEC apoptosis;4.I/R-mediated the up-regulation of autophagy in HUVECs;5.Involvement of MCPIP1 in I/R-mediated the autophagy in HUVECs;6.Autophagy involvement in the cell migration induced by I/R in HUVECs;7.Autophagy involvement in apoptosis induced by I/R in HUVECs.Conclusion:1.I/R-induced MCPIP1 expression regulates the migration and apoptosis of HUVECs and was associated with the up-regulation of autophagy;2.MCPIP1 expression regulates the migration and apoptosis of HUVECs via HMGB1 and CaSR,respectively;3.This study suggest a new therapeutic strategy for individuals with I/R injury.