title: miR-1273g-3p participates in acute glucose fluctuation-induced autophagy, dysfunction, and proliferation attenuation in human umbilical vein endothelial cells.
abstract: Acute glucose fluctuations (AGF) often cause high mortality among critically ill patients, but the mechanisms induced by AGF are not clear. Recent studies suggest that endothelial dysfunction is a key factor that leads to high mortality among critically ill patients. Our goal is to evaluate the phenomenon and mechanisms of endothelial dysfunction induced by AGF. In this study, the functions of human umbilical vein endothelial cells (HUVECs) were compared after treatment with sustained high glucose (SHG), AGF in two groups (AGF1 fluctuations between 5 and 16 mM and AGF2 fluctuations between 5 and 25 mM), and normal glucose levels as a control group (CTR). The medium of the groups was changed every 4 h. The influence of AGF on wound healing was also tested on C57BL/6 mice. The results show that cell proliferation, angiogenesis, and migration functions were injured in the SHG and both AGF groups. AGF2 group shows the worse condition in vitro. In vivo, the wound healing was delayed after the AGF treatment. Furthermore, the markers of apoptosis and autophagy were analyzed. We observed that the autophagy changed in all treatment groups, but apoptosis showed no change. To get to know the mechanism of dysfunction and autophagy, we performed the microRNA chip assay and real-time PCR and found miR-1273g-3p remarkably changed in AGF2 group. After the mimic and inhibitor of miR-1273g-3p were transfected during the AGF2 treatment, we found that the dysfunction and autophagy were partially enhanced by miR-1273g-3p mimic and reversed by miR-1273g-3p inhibitor in AGF2 group. Thus, we conclude that AGF can induce more dysfunction and autophagy, and miR-1273g-3p is also an important factor that leads to the injury.
authors.affiliation: Department of Critical Care Medicine, West China Hospital;
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: College of Life Science; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital;
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Sang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital;
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.affiliation: Department of Critical Care Medicine, West China Hospital;
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: College of Chemical Engineering;
authors.forename: Wenping
authors.initials: W
authors.lastname: Yang
authors.affiliation: West China School of Preclinical and Forensic Medicine; and.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Anesthesia Laboratory, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Critical Care Medicine, West China Hospital; kang_yan_123@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002470:Cell Survival; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D018919:Neovascularization, Physiologic / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*
chemical_list: C000618326:MIRN1273 microRNA, human; D035683:MicroRNAs; D005947:Glucose
keywords: autophagy; endothelial dysfunction; glucose fluctuations; miR-1273g-3p; wound healing