PMID- 18438930 OWN - NLM STAT- MEDLINE DCOM- 20080930 LR - 20181201 IS - 1097-4547 (Electronic) IS - 0360-4012 (Linking) VI - 86 IP - 10 DP - 2008 Aug 1 TI - Brain-derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through MAPK/ERK and PI3K/Akt-dependent signaling pathways. PG - 2168-78 LID - 10.1002/jnr.21669 [doi] AB - Brain-derived neurotrophic factor (BDNF) plays an important role in the differentiation, development, and survival of neural stem cells. In this study, we analyzed its effects on the stimulation of human umbilical cord blood-derived mesenchymal stem cells in terms of their potential to differentiate into neuron-like cells, their survival characteristics, and the molecular mechanisms involved. The treatment of cells with neural induction medium (NIM) and BDNF generated more cells that were neuron-like and produced stronger expression of neural-lineage markers than cells treated with NIM and without BDNF. Raf-1 and ERK phosphorylation and p35 expression levels increased significantly in cells treated with both NIM and BDNF. This treatment also effectively blocked cell death following neural induction and increased Akt phosphorylation and Bcl2 expression compared with cells treated with NIM without BDNF. Inhibition of ERKs inhibited the BDNF-stimulated up-regulation of p35 and Bcl2. In addition, the inhibition of PI3K abrogated Akt phosphorylation and Bcl2 expression, but not p35 expression. Thus, MAPK/ERK-dependent p35 up-regulation and MAPK/ERK-dependent and PI3K/Akt-dependent Bcl2 up-regulation contribute to BDNF-stimulated neural differentiation and to the survival of differentiated cells. FAU - Lim, Jung Yeon AU - Lim JY AD - Department of Neurosurgery, The Catholic University of Korea, Seoul Korea. FAU - Park, Sang In AU - Park SI FAU - Oh, Ji Hyeon AU - Oh JH FAU - Kim, Seong Muk AU - Kim SM FAU - Jeong, Chang Hyun AU - Jeong CH FAU - Jun, Jin Ae AU - Jun JA FAU - Lee, Kwan-Sung AU - Lee KS FAU - Oh, Wonil AU - Oh W FAU - Lee, Jae-Kwon AU - Lee JK FAU - Jeun, Sin-Soo AU - Jeun SS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Tissue Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (neuronal Cdk5 activator (p25-p35)) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Apoptosis/physiology MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cell Differentiation/*physiology MH - Cell Survival/physiology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Fetal Blood/cytology MH - Fluorescent Antibody Technique MH - Gene Expression/physiology MH - Humans MH - Immunohistochemistry MH - In Situ Nick-End Labeling MH - Mesenchymal Stem Cells/*cytology/*metabolism MH - Nerve Tissue Proteins/metabolism MH - Neurons/*cytology/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Signal Transduction/*physiology MH - Up-Regulation EDAT- 2008/04/29 09:00 MHDA- 2008/10/01 09:00 CRDT- 2008/04/29 09:00 PHST- 2008/04/29 09:00 [pubmed] PHST- 2008/10/01 09:00 [medline] PHST- 2008/04/29 09:00 [entrez] AID - 10.1002/jnr.21669 [doi] PST - ppublish SO - J Neurosci Res. 2008 Aug 1;86(10):2168-78. doi: 10.1002/jnr.21669.