title: MiR-21 is overexpressed in response to high glucose and protects endothelial cells from apoptosis.
abstract: Diabetes was an increasing public health problem nowadays. Accumulating evidences had shed a light on the involvement of endothelial cell dysfunction in the pathogenesis of diabetes-associated vascular diseases. MiR-21, a multiple-functional miRNA, was evidenced to be involved in endothelial dysfunction, however, the underlying molecular mechanisms were still unknown. In current study, we investigated the intrinsic link between miR-21 and high glucose-induced endothelial dysfunction. We demonstrated that expression of miR-21 was elevated in circulating endothelial progenitor cells from diabetes patients. Further, inhibition of miR-21 markedly enhanced high glucose-induced endothelial cytotoxicity. Furthermore, proteomic profiling was applied to analyze the downstream effectors involved in miR-21-meidated protection of endothelial cells. A total of 31 proteins were positively identified, including Annexin A2, S100A4, SOD2, Thioredoxin and DAXX. Altered expression of these proteins was validated by immunoblot. Finally, mechanistic study showed that miR-21 protected endothelial cell against high glucose-induced endothelial cytotoxicity probably by inhibiting the expression of DAXX. Our findings were considered as a significant step toward a better understanding of diabetes-associated vascular diseases.
authors.affiliation: Department of Cardiology and Cardiovascular Disease Research Institute, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu City, Sichuan Province, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Zeng
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: He
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Cai
authors.forename: R
authors.initials: R
authors.lastname: Jiang
authors.forename: J
authors.initials: J
authors.lastname: Tao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000096:biosynthesis; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000096:biosynthesis; D013549:Sweetening Agents / Q000494:pharmacology*; D013879:Thioredoxins / Q000096:biosynthesis; D000099156:Superoxide Dismutase 2
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017306:Annexin A2; D056970:Co-Repressor Proteins; D005947:Glucose; D035683:MicroRNAs; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D013482:Superoxide Dismutase; D013549:Sweetening Agents; D013879:Thioredoxins; D000099156:Superoxide Dismutase 2; C472822:ANXA2 protein, human; C106985:DAXX protein, human; C524940:MIRN21 microRNA, human; C077591:S100A4 protein, human