title: Application of recombinant peroxisome proliferator-activated receptor-γ coactivator-1α mediates neovascularization in the retina.
abstract: Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is able to induce the expression of vascular endothelial growth factor (VEGF), promoting the formation of new blood vessels in skeletal muscle. The aim of the current study was to determine whether PGC-1α is able to regulate angiogenesis in human retinal vascular endothelial cells (hRVECs) in vitro and in retinas in vivo. hRVECs treated with recombinant PGC-1α were incubated for 24 h and then placed into a normoxic (20% O2) or hypoxic (1% O2) environment for a further 16 h. Following this, VEGF mRNA and protein levels were significantly increased. Cellular proliferation was enhanced by treatment with recombinant PGC-1α in normoxic and hypoxic conditions. At 24 h following recombinant PGC-1α treatment, hRVECs were plated into Matrigel-coated plates and cultured under normoxic (20% O2) or hypoxic (1% O2) conditions for a further 24 h. Recombinant PGC-1α-treated cells were observed to form significantly greater numbers of tubes. In a C57BL/6J mouse model of ischemic retinopathy, mice received an intravitreal injection of recombinant PGC-1α, resulting in a significant increase in VEGF mRNA and protein levels in the retina. Retinal neovascular tufts and neovascular nuclei were investigated by angiographic and cross-sectional analysis and were observed to be significantly increased in the PGC-1α group compared with the control group. These results indicate that PGC-1α is able to induce angiogenesis in hRVECs and retinas, and suggests that PGC-1α is a potential anti-angiogenic target in retinal neovascularization.
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Xia
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics; D012160:Retina / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D015861:Retinal Neovascularization / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000008:administration & dosage* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A