title: Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) enhances engraftment and angiogenesis of mesenchymal stem cells in diabetic hindlimb ischemia.
abstract: To examine whether the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a key regulator linking angiogenesis and metabolism, could enhance the engraftment and angiogenesis of mesenchymal stem cells (MSCs) in diabetic hindlimb ischemia, we engineered the overexpression of PGC-1α within MSCs using an adenoviral vector encoding green fluorescent protein and PGC-1α, and then tested the survivability and angiogenesis of MSCs in vitro and in vivo. Under the condition of hypoxia concomitant with serum deprivation, the overexpression of PGC-1α in MSCs resulted in a higher expression level of hypoxia-inducible factor-1α (Hif-1α), a greater ratio of B-cell lymphoma leukemia-2 (Bcl-2)/Bcl-2-associated X protein (Bax), and a lower level of caspase 3 compared with the controls, followed by an increased survival rate and an elevated expression level of several proangiogenic factors. In vivo, the MSCs modified with PGC-1α could significantly increase the blood perfusion and capillary density of ischemic hindlimb of the diabetic rats, which was correlated to an improved survivability of MSCs and an increased level of several proangiogenic factors secreted by MSCs. We identified for the first time that PGC-1α could enhance the engraftment and angiogenesis of MSCs in diabetic hindlimb ischemia.
authors.affiliation: Department of Endocrinology and Metabolism, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Debin
authors.initials: D
authors.lastname: Lu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Haihui
authors.initials: H
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Liang
authors.forename: Wuquan
authors.initials: W
authors.lastname: Deng
authors.forename: Youzhao
authors.initials: Y
authors.lastname: Jiang
authors.forename: Qinan
authors.initials: Q
authors.lastname: Wu
authors.forename: Shufa
authors.initials: S
authors.lastname: Li
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ai
authors.forename: Yuxu
authors.initials: Y
authors.lastname: Zhong
authors.forename: Ying
authors.initials: Y
authors.lastname: Ying
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae; D000818:Animals; D048909:Diabetes Complications; D003921:Diabetes Mellitus, Experimental; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000209:etiology / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins