PMID- 24116056 OWN - NLM STAT- MEDLINE DCOM- 20140609 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 10 DP - 2013 TI - The effects of hematopoietic growth factors on neurite outgrowth. PG - e75562 LID - 10.1371/journal.pone.0075562 [doi] LID - e75562 AB - Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are initially discovered as the essential hematopoietic growth factors regulating bone marrow stem cell proliferation and differentiation, and SCF in combination with G-CSF (SCF+G-CSF) has synergistic effects on bone marrow stem cell mobilization. In this study we have determined the effect of SCF and G-CSF on neurite outgrowth in rat cortical neurons. Using molecular and cellular biology and live cell imaging approaches, we have revealed that receptors for SCF and G-CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF synergistically enhances neurite extension through PI3K/AKT and NFkappaB signaling pathways. Moreover, SCF+G-CSF induces much greater NFkappaB activation, NFkappaB transcriptional binding and brain-derived neurotrophic factor (BDNF) production than SCF or G-CSF alone. In addition, we have also observed that BDNF, the target gene of NFkappaB, is required for SCF+G-CSF-induced neurite outgrowth. These data suggest that SCF+G-CSF has synergistic effects to promote neurite growth. This study provides new insights into the contribution of hematopoietic growth factors in neuronal plasticity. FAU - Su, Ye AU - Su Y AD - Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America. FAU - Cui, Lili AU - Cui L FAU - Piao, Chunshu AU - Piao C FAU - Li, Bin AU - Li B FAU - Zhao, Li-Ru AU - Zhao LR LA - eng GR - R01 NS060911/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20131008 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (NF-kappa B) RN - 0 (Receptors, Granulocyte Colony-Stimulating Factor) RN - 0 (Stem Cell Factor) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Cells, Cultured MH - Cerebral Cortex/cytology/*drug effects/metabolism MH - Granulocyte Colony-Stimulating Factor/*pharmacology MH - NF-kappa B/metabolism MH - Neurites/*drug effects/metabolism MH - Neurons/cytology/*drug effects/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Proto-Oncogene Proteins c-kit/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Granulocyte Colony-Stimulating Factor/metabolism MH - Signal Transduction/drug effects/physiology MH - Stem Cell Factor/*pharmacology PMC - PMC3792965 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/10/12 06:00 MHDA- 2014/06/10 06:00 PMCR- 2013/10/08 CRDT- 2013/10/12 06:00 PHST- 2013/06/11 00:00 [received] PHST- 2013/08/14 00:00 [accepted] PHST- 2013/10/12 06:00 [entrez] PHST- 2013/10/12 06:00 [pubmed] PHST- 2014/06/10 06:00 [medline] PHST- 2013/10/08 00:00 [pmc-release] AID - PONE-D-13-24203 [pii] AID - 10.1371/journal.pone.0075562 [doi] PST - epublish SO - PLoS One. 2013 Oct 8;8(10):e75562. doi: 10.1371/journal.pone.0075562. eCollection 2013.