Epidermal growth factor increases the expression of Nestin in rat reactive astrocytes through the Ras-Raf-ERK pathway.
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 PLCγ, PI3K, 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.
Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Wei-Lu
WL
Gao
Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Feng
F
Tian
Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei 230032, China.
Sheng-Quan
SQ
Zhang
Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Hui
H
Zhang
Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address: yinzs1961@163.com.
Zong-Sheng
ZS
Yin
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D064231:Nestin / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D048490:raf Kinases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D007381:Intermediate Filament Proteins; D064231:Nestin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D048490:raf Kinases; D018631:ras Proteins
Astrocyte; ErbB1; Nestin; Signal transduction