PMID- 23000062 OWN - NLM STAT- MEDLINE DCOM- 20130722 LR - 20181202 IS - 1872-8111 (Electronic) IS - 0168-0102 (Linking) VI - 74 IP - 3-4 DP - 2012 Dec TI - Pleiotrophin promotes microglia proliferation and secretion of neurotrophic factors by activating extracellular signal-regulated kinase 1/2 pathway. PG - 269-76 LID - S0168-0102(12)00173-3 [pii] LID - 10.1016/j.neures.2012.09.001 [doi] AB - 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-alpha, IL-1beta 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. CI - Copyright (c) 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved. FAU - Miao, Jiayin AU - Miao J AD - Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University, The 2nd Zhongshan Road, GuangZhou 510080, China. FAU - Ding, Minghui AU - Ding M FAU - Zhang, Aiwu AU - Zhang A FAU - Xiao, Zijian AU - Xiao Z FAU - Qi, Weiwei AU - Qi W FAU - Luo, Ning AU - Luo N FAU - Di, Wei AU - Di W FAU - Tao, Yuqian AU - Tao Y FAU - Fang, Yannan AU - Fang Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120918 PL - Ireland TA - Neurosci Res JT - Neuroscience research JID - 8500749 RN - 0 (Carrier Proteins) RN - 0 (Cytokines) RN - 0 (Nerve Growth Factors) RN - 134034-50-7 (pleiotrophin) SB - IM MH - Animals MH - Blotting, Western MH - Carrier Proteins/*metabolism MH - Cell Proliferation MH - Cytokines/*metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Immunohistochemistry MH - MAP Kinase Signaling System/*physiology MH - Microglia/*metabolism MH - Nerve Growth Factors/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2012/09/25 06:00 MHDA- 2013/07/23 06:00 CRDT- 2012/09/25 06:00 PHST- 2012/07/12 00:00 [received] PHST- 2012/08/23 00:00 [revised] PHST- 2012/09/03 00:00 [accepted] PHST- 2012/09/25 06:00 [entrez] PHST- 2012/09/25 06:00 [pubmed] PHST- 2013/07/23 06:00 [medline] AID - S0168-0102(12)00173-3 [pii] AID - 10.1016/j.neures.2012.09.001 [doi] PST - ppublish SO - Neurosci Res. 2012 Dec;74(3-4):269-76. doi: 10.1016/j.neures.2012.09.001. Epub 2012 Sep 18.