Activation of epidermal growth factor receptor causes astrocytes to form cribriform structures

• Published in: Glia 2004-04, Vol.46 (2), p.153-168
• Main Authors: Liu, Bin, Neufeld, Arthur H.
• Format: Article
• Language: English
• Subjects: Adult; astrocyte; Astrocytes - cytology; Astrocytes - metabolism; Biological and medical sciences; cavitation; Cell Communication - drug effects; Cell Communication - physiology; Cell Division - drug effects; Cell Division - physiology; Cell Movement - drug effects; Cell Movement - physiology; Cells, Cultured; Cicatrix - metabolism; Cicatrix - pathology; Cytoskeleton - metabolism; Epidermal Growth Factor - pharmacology; epidermal growth factor receptor; extracellular matrix; Extracellular Space - metabolism; Eye and associated structures. Visual pathways and centers. Vision; Fibronectins - metabolism; Fundamental and applied biological sciences. Psychology; Glaucoma - metabolism; Glaucoma - pathology; Humans; Integrin beta1 - metabolism; Isolated neuron and nerve. Neuroglia; Middle Aged; migration; Optic Disk - cytology; optic nerve; Receptor, Epidermal Growth Factor - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.10358

Epidermal growth factor receptor (EGFR) is expressed in reactive astrocytes following injury in the CNS. However, the effects of activation of the EGFR pathway in astrocytes are not well established. In the present study, we demonstrate that activation of EGFR causes optic nerve astrocytes, as well as brain astrocytes, to form cribriform structures with cavernous spaces. Formation of the cribriform structures is dependent on new protein synthesis and cell proliferation. Platelet‐derived growth factor and basic fibroblast growth factor were not effective. Smooth muscle cells and epithelial cells do not form cribriform structures in response to EGFR activation. The formation of the cribriform structures appears to be related to a guided migration of astrocytes and the expression of integrin β1 and extracellular fibronectin in response to activation of EGFR. The EGFR pathway may be a specific, signal transduction pathway that regulates reactive astrocytes to form cavernous spaces in the glial scars following CNS injury and in the compressed optic nerve in glaucomatous optic nerve neuropathy. © 2004 Wiley‐Liss, Inc.