title: Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and -catenin pathway after spinal cord injury.
abstract: Aberrant functionality of the cell cycle has been implicated in the pathology of traumatic SCI. Although it has been reported that the expressions of various cell cycle related proteins were altered significantly following SCI, detailed information on the subject remains largely unclear. The embryonic pyruvate kinase M2 (PKM2) is an important metabolic kinase in aerobic glycolysis or the warburg effect, however, its functions in central nervous system (CNS) injury remains elusive. Here we demonstrate that PKM2 was not only significantly upregulated by western blot and immunohistochemistry but certain traumatic stimuli also induced translocation of PKM2 into the nucleus in astrocytes following spinal cord injury (SCI). Furthermore, the expression levels and localization of p-β-catenin, p27, cyclin D1 and PCNA were correlated with PKM2 after SCI. In vitro, we also found that PKM2 co-immunoprecipitation with p-β-catenin and p27 respectively. Knockdown of PKM2 apparently decreased the level of PCNA, cyclinD1, p27 in primary astrocyte cells. Taken together, our findings indicate that nuclear translocation of PKM2 promotes astrocytes proliferation after SCI through modulating cell cycle signaling. These discoveries firstly uncovered the role of PKM2 in spinal cord injury and provided a potential therapeutic target for CNS injury and repair.
authors.affiliation: a Department of Spine Surgery ; The Second Affiliated Hospital of Nantong University; Nantong University ; 226001 , Nantong, Jiangsu , PR , China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhang
authors.forename: Guijuan
authors.initials: G
authors.lastname: Feng
authors.forename: Guofeng
authors.initials: G
authors.lastname: Bao
authors.forename: Guanhua
authors.initials: G
authors.lastname: Xu
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Sun
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.forename: Lingling
authors.initials: L
authors.lastname: Wang
authors.forename: Jiajia
authors.initials: J
authors.lastname: Chen
authors.forename: Huricha
authors.initials: H
authors.lastname: Jin
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cui
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D015870:Gene Expression; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009928:Organ Specificity; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000276:immunology / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins
keywords: PKM2; astrocyte proliferation; p27; spinal cord injury; β-catenin