Activation of epidermal growth factor receptor causes astrocytes to form cribriform structures.
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 beta1 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.
Liu
Bin
B
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA. liu@vision.wustl.edu
Neufeld
Arthur H
AH
D000328:Adult; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008875:Middle Aged; D009898:Optic Disk / Q000166:cytology
D005353:Fibronectins; D019012:Integrin beta1; D004815:Epidermal Growth Factor; D066246:ErbB Receptors