CHIA-LUN CHAOChuang, Chun-PinChun-PinChuangCheng, Yen-FenYen-FenChengLee, Kueir-RarnKueir-RarnLeeChang, YungYungChangCheng, Shun-PingShun-PingChengChan, Wan-KheyWan-KheyChanHo, Feng-MingFeng-MingHo2023-09-082023-09-082016-0403603997https://www.scopus.com/record/display.uri?eid=2-s2.0-84957583360&origin=inward&txGid=4583170f71c25ebf4c4cbe41c08a7c67https://scholars.lib.ntu.edu.tw/handle/123456789/635258Diabetes mellitus may cause vascular endothelial damage via endothelial matrix metalloproteinase-2 (MMP-2). The role of endothelial autophagy in MMP-2-mediated cell injury in response to high-glucose (HG) stimulation was rarely described. In this study, we used HG-treated human umbilical vein endothelial cells (HUVECs) to investigate the effect of autophagy on MMP-2-induced cell transmigration and apoptosis. THP-1 transmigration was detected by the transmigration assay. Light chain 3 (LC3, representing autophagy), MMP-2, and poly (ADP-ribose) polymerase (PARP, representing apoptosis) of HG (33 mM)-treated HUVECs were evaluated by western blot analysis. The MMP-2 activity was also examined by gelatin zymography. We used GM6001 (10 μM, an MMP-2 inhibitor) to investigate the relationship of MMP-2 and THP-1 transmigration. Using 3-methyladenine (3MA, 5 mM, an LC3 inhibitor), we explored the effects of autophagy on MMP-2 expression, THP-1 transmigration, and apoptosis. Our results showed that HG increased LC3-II expression, MMP-2 activity, THP-1 transmigration, and cleaved PARP expression in a time-dependent manner (0-48 h); among them, LC3-II appeared earlier (0-24 h) than the others (24-48 h). GM6001 suppressed MMP-2 activity and ameliorated THP-1 transmigration. 3MA suppressed LC3-II expression and increased MMP-2 expression, THP-1 transmigration, and cleaved PARP expression. From these sequential findings, we demonstrated that autophagy plays a protective role in MMP-2-mediated cell transmigration and cell death in HG-stimulated HUVECs.enautophagy; endothelial cells; high glucose; matrix metalloproteinase; transmigrationThe Protective Role of Autophagy in Matrix Metalloproteinase-Mediated Cell Transmigration and Cell Death in High-Glucose-Treated Endothelial Cellsjournal article10.1007/s10753-016-0313-7268468842-s2.0-84957583360https://api.elsevier.com/content/abstract/scopus_id/84957583360