title: Cdc42 Promotes Schwann Cell Proliferation and Migration Through Wnt/β-Catenin and p38 MAPK Signaling Pathway After Sciatic Nerve Injury.
abstract: Schwann cells (SCs) are unique glial cells in the peripheral nerve and may secrete multiple neurotrophic factors, adhesion molecules, extracellular matrix molecules to form the microenvironment of peripheral nerve regeneration, guiding and supporting nerve proliferation and migration. Cdc42 plays an important regulatory role in dynamic changes of the cytoskeleton. However, there is a little study referred to regulation and mechanism of Cdc42 on glial cells after peripheral nerve injury. The present study investigated the role of Cdc42 in the proliferation and migration of SCs after sciatic nerve injury. Cdc42 expression was tested, showing that the mRNA and protein expression levels of Cdc42 were significantly up-regulated after sciatic nerve injury. Then, we isolated and purified SCs from injuried sciatic nerve at day 7. The purified SCs were transfected with Cdc42 siRNA and pcDNA3.1-Cdc42, and the cell proliferation, cell cycle and migration were assessed. The results implied that Cdc42 siRNA remarkably inhibited Schwann cell proliferation and migration, and resulted in S phase arrest. While pcDNA3.1-Cdc42 showed a contrary effect. Besides, we also observed that Cdc42 siRNA down-regulated the protein expression of β-catenin, Cyclin D1, c-myc and p-p38, which were up-regulated by pcDNA3.1-Cdc42. Meanwhile, the inhibitor of Wnt/β-catenin and p38 MAPK signaling pathway IWP-2 and SB203580 significantly inhibited the effect of pcDNA3.1-Cdc42 on cell proliferation and migration. Overall, our data indicate that Cdc42 regulates Schwann cell proliferation and migration through Wnt/β-catenin and p38 MAPK signaling pathway after sciatic nerve injury, which provides further insights into the therapy of the sciatic nerve injury.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xi'an Medical University, 48 Feng hao Road, Xi'an, 710077, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xi'an Medical University, 48 Feng hao Road, Xi'an, 710077, China.
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xi'an Medical University, 48 Feng hao Road, Xi'an, 710077, China.
authors.forename: Wu-Tao
authors.initials: WT
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xi'an Medical University, 48 Feng hao Road, Xi'an, 710077, China.
authors.forename: Zheng-Wei
authors.initials: ZW
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xi'an Medical University, 48 Feng hao Road, Xi'an, 710077, China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: He
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xi'an Medical University, 48 Feng hao Road, Xi'an, 710077, China. Songxiaoyang_9896@163.com.
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Song
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C495268:Ctnnb1 protein, rat; D051176:beta Catenin; D048051:p38 Mitogen-Activated Protein Kinases; D020764:cdc42 GTP-Binding Protein
keywords: Cdc42; Migration; Schwann cell; Sciatic nerve injury