Granulocyte colony-stimulating factor improves neuron survival in experimental spinal cord injury by regulating nucleophosmin-1 expression.
Granulocyte colony-stimulating factor (G-CSF) and its related mechanisms were investigated to assess the potential for this factor to exert neuroprotective effects against spinal cord injury in mice. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was injected into mice spinal cord hemisection models. Locomotor activity was assessed by using the Basso-Bettie-Bresnahan scale. Neurons isolated from spinal cords were cultured in vitro and used in a neuronal mechanical injury model. Three treatment groups were compared with this model, 1) G-CSF, 2) G-CSF + NSC348884 (a nucleophosmin 1-specific inhibitor), and 3) NSC348884. Immunofluorescence staining and Western blotting were performed to analyze the expression of G-CSF and nucleophosmin 1 (Npm1). TUNEL staining was performed to analyze apoptosis after G-CSF treatment. We found that the G-CSF receptor (G-CSFR) and Npm1 were expressed in neurons and that Npm1 expression was induced after G-CSF treatment. G-CSF inhibited neuronal apoptosis. NSC348884 induced p53-dependent cell apoptosis and partially blocked the neuroprotective activity of G-CSF on neurons in vitro. G-CSF promoted locomotor recovery and demonstrated neuroprotective effects in an acute spinal cord injury model. The mechanism of G-CSF's neuroprotection may be related in part to attenuating neuronal apoptosis by NPM1.
Yuji
Y
Guo
Shangming
S
Liu
Ping
P
Wang
Hui
H
Zhang
Fuwu
F
Wang
Lujun
L
Bing
Jiangang
J
Gao
Jie
J
Yang
Aijun
A
Hao
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis*; D000090243:Nucleophosmin; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology
C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D000090243:Nucleophosmin; D016179:Granulocyte Colony-Stimulating Factor