Journal article
MicroRNA miR-27b Rescues Bone Marrow-Derived Angiogenic Cell Function and Accelerates Wound Healing in Type 2 Diabetes Mellitus
Arteriosclerosis, thrombosis, and vascular biology, Vol.34(1), pp.99-109
01/01/2014
DOI: 10.1161/ATVBAHA.113.302104
PMCID: PMC5533613
PMID: 24177325
Abstract
Objective-Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice.
Approach and Results-BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice.
Conclusions-miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.
Details
- Title: Subtitle
- MicroRNA miR-27b Rescues Bone Marrow-Derived Angiogenic Cell Function and Accelerates Wound Healing in Type 2 Diabetes Mellitus
- Creators
- Jie-Mei Wang - University of PittsburghJun Tao - VA Pittsburgh Healthcare SystemDan-Dan Chen - First Affiliated Hospital of Sun Yat-sen UniversityJing-Jing Cai - Cent South Univ, Dept Cardiol, Changsha 410013, Hunan, Peoples R ChinaKaikobad Irani - Roy J. and Lucille A. Carver College of MedicineQinde Wang - Central-South UniversityHong Yuan - Central-South UniversityAlex F. Chen - Central-South University
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.34(1), pp.99-109
- Publisher
- Lippincott Williams & Wilkins
- DOI
- 10.1161/ATVBAHA.113.302104
- PMID
- 24177325
- PMCID
- PMC5533613
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Number of pages
- 30
- Grant note
- R01 GM077352 / National Institutes of Health (NIH)/National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 7-11-BS-23 / American Diabetes Association R21CA158650 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01GM077352 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 81130004 / National Science Foundation of China; National Natural Science Foundation of China (NSFC) 1R21CA158650 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 20070320 / China Overseas Scholarship I01RX000244; 1I01RX000652 / Department of Veterans Affairs; US Department of Veterans Affairs 0920110G; 13SDG16930098 / American Heart Association I01RX000652 / Veterans Affairs; US Department of Veterans Affairs
- Language
- English
- Date published
- 01/01/2014
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984313077402771
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