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Glucocorticoid inhibits growth factor‐induced differentiation of hippocampal progenitor HiB5 cells
Author(s) -
Son Gi Hoon,
Geum Dongho,
Jung Hosung,
Kim Kyungjin
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00634.x
Subject(s) - glucocorticoid receptor , glucocorticoid , platelet derived growth factor receptor , signal transduction , microbiology and biotechnology , medicine , endocrinology , biology , mapk/erk pathway , creb , protein tyrosine phosphatase , progenitor cell , tyrosine phosphorylation , cellular differentiation , chemistry , growth factor , transcription factor , receptor , stem cell , biochemistry , gene
In the present study, we investigated the effect of glucocorticoid on neuronal differentiation of hippocampal progenitor HiB5 cells. Dexamethasone (DEX), a synthetic glucocorticoid, inhibited platelet‐derived growth factor (PDGF)‐induced differentiation of HiB5 cells. The inhibitory effect of DEX was antagonized by RU486, a glucocorticoid receptor (GR) antagonist, indicating the GR‐mediated processes. Nestin mRNA level was decreased and midsize neurofilament (NF‐M) mRNA level was increased as a function of neuronal differentiation. DEX significantly blocked PDGF‐induced down‐regulation of nestin mRNA level, and up‐regulation of NF‐M mRNA level, which were similar to those of undifferentiated cells. DEX inhibited PDGF‐induced activation of cyclic AMP‐responsive element binding protein (CREB) and AP‐1, suggesting that glucocorticoid interfered with signal transduction cascades linking the PDGF receptor and downstream transcription factors. Indeed, DEX reduced PDGF‐induced phosphorylation of extracellular signal‐regulated kinases1/2 (ERK1/2). Tyrosine phosphatase inhibitor reversed the effect of DEX on ERK1/2. In accordance with this finding, blockage of ERK1/2 signaling pathway with PD098059, a potent inhibitor for Ras/ERK pathway, mimicked the inhibitory effect of DEX on differentiation processes. Taken together, these results indicate that glucocorticoid inhibits PDGF‐induced differentiation of hippocampal progenitor HiB5 cells by inhibiting the ERK1/2 signaling cascade via a tyrosine phosphatase‐dependent mechanism.