title: FoxM1 involvement in astrocyte proliferation after spinal cord injury in rats.
abstract: The Forkhead box M1 (FoxM1) protein is a proliferation-associated transcription factor that plays a key role in controlling both the G1/S and G2/M transitions of the cell cycle and regulates transcription of cell cycle genes, including cyclin-dependent kinase inhibitors p27(kip1) and p21(waf1/cip1). The expression levels of FoxM1 directly correlated with the proliferation index, cancer survival, genomic instability rate, and microvessel density, and inversely correlated with apoptosis. Furthermore, FoxM1 is determined to play a role in tissue repair following injury in the lungs and liver. However, the signaling of FoxM1, involved in its expression and its role in central nervous system lesion and repair is poorly known. In this study, we performed a spinal cord injury (SCI) model in adult Sprague-Dawley rats and investigated the dynamic changes and role of FoxM1 expression in the spinal cord. Western blot analysis revealed that FoxM1 was lowly presented in normal spinal cord. It gradually increased, reached a peak at day 3, and then declined to basal levels at 14 days after spinal cord injury. Immunohistochemistry further confirmed that FoxM1 was expressed at low levels in gray and white matters in normal condition and increased after SCI. Double immunofluorescence staining showed that FoxM1was co-expressed with NeuN (neuronal marker) and GFAP (astrocytic marker), and FoxM1 expression was increased predominantly in astrocytes after injury, which were regenerating axons and largely proliferated after injury. Furthermore, co-immunoprecipitation studies demonstrated increased interactions among FoxM1, Skp2, and p27(kip1) in the spinal cord after injury. Taken together, these results provide new insights into the molecular mechanisms underlying astrocyte proliferation during SCI and suggest that FoxM1 might play crucial roles in CNS pathophysiology after SCI.
authors: Department of Orthopaedics, The Central Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, 050011, People's Republic of China.
authors: Shuangwei
authors: S
authors: Zhang
authors: Honglin
authors: H
authors: Teng
authors: Qiulei
authors: Q
authors: Ding
authors: Jinpeng
authors: J
authors: Fan
authors: Wanying
authors: W
authors: Shi
authors: Yan
authors: Y
authors: Zhou
authors: Chunwu
authors: C
authors: Zhang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology; D001369:Axons / Q000378:metabolism; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: C493962:Cdkn1b protein, rat; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C513169:Foxm1 protein, rat; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27
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