Journal
NEUROSCIENCE LETTERS
Volume 562, Issue -, Pages 54-59Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2014.01.018
Keywords
Astrocyte; ErbB1; Nestin; Signal transduction
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Funding
- National Nature Science Foundation of China [30973026]
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Astrocytes undergo de-differentiation and become activated during a response to injury. Several studies have found that reactive astrocytes re-express markers, such as Nestin, which are normally expressed in neural stem cells. It was recently shown that the epidermal growth factor receptor (EGFR) is up-regulated in astrocytes after injury and promotes reactive astrocyte transformation. However, the signaling pathways involved in this process have not been elucidated. In the present study, we showed that Nestin was strongly expressed in reactive astrocytes. Furthermore, as shown by immunoblot analyses, epidermal growth factor (EGF) regulated Nestin expression through EGFR activation. Inhibition of the PLC gamma, PI3 K, ERK, p38, and JNK pathways did not affect Nestin expression in reactive astrocytes. However, treatment with a Raf-1 inhibitor inhibited Nestin expression in a concentration-dependent manner. Taken together, the signaling analyses revealed that EGF induced and regulated Nestin expression through activation of the Ras-Raf-ERK signaling pathway. This is the first study to show that Nestin expression is regulated by an extracellular signaling molecule in reactive astrocytes. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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