Application of recombinant peroxisome proliferator-activated receptor-γ coactivator-1α mediates neovascularization in the retina

作者：Jiang, Jian; Zhang, Lixin; Zhang, Lu; Xia, Xiaobo^*

来源：Molecular Medicine Reports, 2016, 13(2): 1311-1319.

DOI：10.3892/mmr.2015.4678

• peroxisome proliferator-activated receptor-gamma
• coactivator-1 alpha
• vascular endothelial growth factor
• recombinant protein
• retinal vascular endothelial cell
• retinal neovascularization

Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) 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-1 alpha is able to regulate angiogenesis in human retinal vascular endothelial cells (hRVECs) in vitro and in retinas in vivo. hRVECs treated with recombinant PGC-1 alpha were incubated for 24 h and then placed into a normoxic (20% O-2) or hypoxic (1% O-2) environment for a further 16 h. Following this, VEGF mRNA and protein levels were significantly increased. Cellular prolie eration was enhanced by treatment with recombinant PGC-1 alpha in normoxic and hypoxic conditions. At 24 h following recombinant PGC-1 alpha treatment, hRVECs were plated into Matrigel-coated plates and cultured under normoxic (20% 02) or hypoxic (1% 07) conditions for a further 24 h. Recombinant PGC-1 alpha-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-1 alpha, 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-1 alpha group compared with the control group. These results indicate that PGC-1 alpha is able to induce angiogenesis in hRVECs and retinas, and suggests that PGC-1 alpha is a potential anti-angiogenic target in retinal neovascularization.

• 出版日期2016-2
• 单位中南大学