Expression of HB-EGF by retinal pigment epithelial cells in vitreoretinal proliferative disease

Hollborn, Margrit; Iandiev, Ianors; Seifert, Marlen; Schnurrbusch, Ute E K; Wolf, Sebastian; Wiedemann, Peter; Bringmann, Andreas; Kohen, Leon (2006). Expression of HB-EGF by retinal pigment epithelial cells in vitreoretinal proliferative disease. Current eye research, 31(10), pp. 863-74. New York, N.Y.: Informa Healthcare 10.1080/02713680600888807

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The heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been implicated in wound-healing processes of various tissues. However, it is not known whether HB-EGF may represent a factor implicated in overstimulated wound-healing processes of the retina during proliferative retinopathies. Therefore, we investigated whether human retinal pigment epithelial (RPE) cells, which are crucially involved in proliferative retinopathies, express and respond to HB-EGF. RPE cells express mRNAs for various members of the EGF-related growth factor family, among them for HB-EGF, as well as for the EGF receptors ErbB1, -2, -3, and -4. The gene expression of HB-EGF is stimulated in the presence of transforming and basic fibroblast growth factors and by oxidative stress and is suppressed during chemical hypoxia. Exogenous HB-EGF stimulates proliferation and migration of RPE cells and the gene and protein expression of the vascular endothelial growth factor (VEGF). HB-EGF activates at least three signal transduction pathways in RPE cells including the extracellular signal-regulated kinases (involved in the proliferation-stimulating action of HB-EGF), p38 (mediates the effects on chemotaxis and secretion of VEGF), and the phosphatidylinositol-3 kinase (necessary for the stimulation of chemotaxis). In epiretinal membranes of patients with proliferative retinopathies, HB-EGF immunoreactivity was partially colocalized with the RPE cell marker, cytokeratins; this observation suggests that RPE cell-derived HB-EGF may represent one factor that drives the uncontrolled wound-healing process of the retina. The stimulating effect on the secretion of VEGF may suggest that HB-EGF is also implicated in the pathological angiogenesis of the retina.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology
UniBE Contributor:	Wolf, Sebastian (B)
ISSN:	0271-3683
ISBN:	17050278
Publisher:	Informa Healthcare
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:49
Last Modified:	05 Dec 2022 14:15
Publisher DOI:	10.1080/02713680600888807
PubMed ID:	17050278
Web of Science ID:	000241196200008
URI:	https://boris.unibe.ch/id/eprint/20450 (FactScience: 3748)