title: Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p.
abstract: Ischemic preconditioning (IPC) has protective effects against ischemia-perfusion injury of organs. In the present study, we investigated the associated mechanisms after performing remote IPC (rIPC) of lower limbs by clamping abdominal aorta in mice. Subsequent experiments showed decreased damage and paralysis of lower limbs following spinal cord injury (SCI). Concomitantly, plasma vascular endothelial growth factor (VEGF) levels were increased 24 h after rIPC compared with those in sham-operated animals. In subsequent microRNA analyses, thirteen microRNAs were downregulated in exosomes 24 h after rIPC. Further studies of femoral CD34-positive bone marrow (BM) cells confirmed downregulation of these seven microRNAs 24 h after rIPC compared with those in sham-operated controls. Subsequent algorithm-based database searches suggested that two of the seven microRNAs bind to the 3' UTR of VEGF mRNA, and following transfection into CD34-positive BM cells, anti-miR-762, and anti-miR-3072-5p inhibitors led to increased VEGF concentrations. The present data suggest that rIPC transiently increases plasma VEGF levels by downregulating miR-762 and miR-3072-5p in CD34-positive BM cells, leading to protection against organ ischemia.
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Center for Regenerative Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Samura
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Kawamura
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Center for Regenerative Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Hosoyama
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Morikage
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D015536:Down-Regulation; D055354:Exosomes / Q000378:metabolism*; D007511:Ischemia / Q000097:blood / Q000517:prevention & control; D019194:Ischemic Preconditioning; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse