title: Pleiotrophin promotes microglia proliferation and secretion of neurotrophic factors by activating extracellular signal-regulated kinase 1/2 pathway.
abstract: Pleiotrophin (PTN) is an effective neuroprotective factor and its expression is strikingly increased in microglia after ischemia/reperfusion injury. However, whether PTN could provide neurotrophic support to neurons by regulating microglia function is not clear. In this study, we demonstrated that the expression of PTN was induced in microglia after oxygen-glucose deprivation/reperfusion. PTN promoted the proliferation of microglia by enhancing the G1 to S phase transition. PTN also stimulated the secretion of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and nerve growth factor (NGF) in microglia, but did not upregulate the expression of proinflammatory factors such as TNF-α, IL-1β and iNOS. Mechanistically, we found that PTN increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in microglia in both concentration-dependent and time-dependent manners. In addition, ERK1/2 inhibitor U0126 abolished the proliferation and G1 to S phase transition of microglia stimulated by PTN, and inhibited the production of BDNF, CNTF and NGF induced by PTN. In conclusion, our results demonstrated that PTN-ERK1/2 pathway plays important role in regulating microglia growth and secretion of neurotrophic factors. These findings provide new insight into the neuroprotective role of PTN and suggest that PTN is a new target for therapeutic intervention of stroke.
authors.affiliation: Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University, The 2nd Zhongshan Road, GuangZhou 510080, China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Miao
authors.forename: Minghui
authors.initials: M
authors.lastname: Ding
authors.forename: Aiwu
authors.initials: A
authors.lastname: Zhang
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xiao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qi
authors.forename: Ning
authors.initials: N
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Di
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Tao
authors.forename: Yannan
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000502:physiology*; D017628:Microglia / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D009414:Nerve Growth Factors; C066845:pleiotrophin