title: Overexpression of mitofusin 2 inhibits reactive astrogliosis proliferation in vitro.
abstract: Astrocytes become activated in response to central nervous system (CNS) injury, and excessive astrogliosis is considered an impediment to axonal regeneration by forming glial scar. Mitofusin 2 (Mfn2), a key protein in mitochondrial network, has been reported to negatively regulate cell proliferation. The present study aimed to explore whether reactive astrogliosis could be suppressed by Mfn2 overexpression. Scratch injury and starvation-serum stimulation models in cultured astrocytes were combined to address this issue. In scratch model, reactive proliferation status of damaged astrocytes was implicated by migration of high ratio of EdU(+) cells into lesion region and significantly increased expression of GFAP and PCNA. At meantime, Mfn2 expression was found to exert a down-regulated trend both in gen and protein levels. Pretreatment of cells with adenoviral vector encoding Mfn2 gene increased Mfn2 expression and subsequently attenuated injury-induced astrocytes hyperplasia, activation-relevant protein synthesis, cellular proliferation, eventually delayed wound healing process. Furthermore, Mfn2 overexpression markedly inhibited astrocytes proliferation induced by serum stimulation, by arresting the transition of cell cycle from G1 to S phase. Together, these in vitro results demonstrated that reactive astrogliosis can be effectively suppressed by up-regulation of Mfn2, which might contribute to a promising therapeutic intervention in CNS disease characterized by glia-related damage.
authors.affiliation: Department of Traumatic Surgery, Tong-ji Hospital, Tong-ji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Traumatic Surgery, Tong-ji Hospital, Tong-ji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chen-chen
authors.initials: CC
authors.lastname: Xue
authors.affiliation: Department of Traumatic Surgery, Tong-ji Hospital, Tong-ji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu-long
authors.initials: YL
authors.lastname: Shi
authors.affiliation: Department of Traumatic Surgery, Tong-ji Hospital, Tong-ji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiang-jun
authors.initials: XJ
authors.lastname: Bai
authors.affiliation: Department of Traumatic Surgery, Tong-ji Hospital, Tong-ji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhan-fei
authors.initials: ZF
authors.lastname: Li
authors.affiliation: Department of Traumatic Surgery, Tong-ji Hospital, Tong-ji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: chenglayi@163.com.
authors.forename: Cheng-la
authors.initials: CL
authors.lastname: Yi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum; D014945:Wound Healing
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat
keywords: Cell cycle arrest; Mitofusin 2; Reactive astrogliosis