title: The effect of estrogen-related receptor α on the regulation of angiogenesis after spinal cord injury.
abstract: Estrogen receptor-related receptor-α (ERRα) is an orphan member of the nuclear receptor superfamily that interacts with peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) to stimulate vascular endothelial growth factor (VEGF) expression and angiogenesis in a hypoxia-inducible factor-1α-independent pathway. Although it is not regulated by any natural ligand, the action of ERRα can be blocked by the synthetic molecule XCT790. In the present study, Sprague-Dawley rats were randomly allocated to a sham group, injury-saline group or injury-XCT90 group. A modified Allen's weight-drop method was applied to induce the acute traumatic spinal cord injury (SCI) model in these rats, and an injection of XCT790 was administered every 24h, starting half an hour after the SCI contusion. Histological analyses revealed that XCT790 significantly aggravated tissue damage and decreased the number of ERRα-positive cells at 1, 3 and 7 days after SCI. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analyses also indicated that XCT790 dramatically repressed the expression of ERRα, thus reducing the expression of VEGF and angiopoietin-2 (Ang-2) throughout the duration of the experiment, but the expression of PGC-1α was not affected. Immunofluorescence analyses indicated that vascular density and endothelial cell proliferation were decreased in the injury-XCT90 group compared with the injury-saline group. These results suggest that ERRα is involved in mediating angiogenesis after SCI in the rat traumatic SCI model.
authors: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors: J Z
authors: JZ
authors: Hu
authors: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors: H
authors: H
authors: Long
authors: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors: T-D
authors: TD
authors: Wu
authors: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors: Y
authors: Y
authors: Zhou
authors: Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha 410008, PR China. Electronic address: hongbinlu@hotmail.com.
authors: H-B
authors: HB
authors: Lu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009570:Nitriles / Q000494:pharmacology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013844:Thiazoles / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D020533:Angiogenesis Inhibitors; D042702:Angiopoietin-2; D009570:Nitriles; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D013844:Thiazoles; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000097983:ERRalpha Estrogen-Related Receptor; C501429:Ppargc1a protein, rat; C488234:XCT790; C467498:vascular endothelial growth factor A, rat
keywords: XCT790; angiogenesis; estrogen receptor-related receptor-α; spinal cord injury