title: VEGF inhibits the inflammation in spinal cord injury through activation of autophagy.
abstract: Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis and re-vascularization of spinal cord injury (SCI). VEGF has long been thought to be a potent neurotrophic factor for the survival of spinal cord neuron. However, the neuroprotective mechanism of VEGF is still unclear. The aim of this study was to investigate the effect of VEGF on spinal cord injury and its mechanisms. Young male Wistar rats were subjected to SCI and then VEGF165 were injected directly into the lesion epicenter 24 h post injury. We detected Basso, Beattie and Bresnahan (BBB) scores and numbers of motor neuron via Nissl staining. The expressions of autophagy related protein Beclin1 and LC3B were determined by Western blot and RT-PCR. We also detected the contents of inflammation factors interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-10(IL-10) in LPS (Lipopolysaccharide) treated spinal neuron-glia co-culture by ELISA. We found that VEGF165 administration increased the BBB score and reduced the loss of motor neuron of rats induced by SCI. VEGF decreased the protein expressions of IL-1β, TNF-α and IL-10 and up-regulated the expressions of Beclin1 and LC3B of rats. In the in vitro study, VEGF165 decreased the levels of IL-1β, IL-10 and TNF-a in the medium of LPS treated spinal neuron-glia co-culture, which was partially blocked by 3-MA, the inhibitor of autophagy. In addition, VEGF165 up-regulate the expressions of Beclin1 and LC3B in co-culture cells. The results suggested that VEGF165 attenuated the spinal cord injury by inhibiting the inflammation and increasing the autophagy function.
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou City, PR China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou City, PR China.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou City, PR China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou City, PR China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Second Affiliated Hospital of Liaoning Medical University, Jinzhou City, PR China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Liaoning Medical University, Jinzhou City, PR China.
authors.forename: Donghe
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou City, PR China.
authors.forename: Yajiang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Liaoning Medical University, Jinzhou City, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou City, PR China. Electronic address: meixifan1971@163.com.
authors.forename: Xifan
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D018920:Coculture Techniques; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000150:complications* / Q000276:immunology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; D042461:Vascular Endothelial Growth Factor A; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat
keywords: Autophagy; Spinal cord injury; TNF-α; VEGF