Signaling pathways involved in PDGF-evoked cellular responses in human RPE cells.
We examined whether PDGF may directly stimulate the expression of VEGF by retinal pigment epithelial (RPE) cells in vitro, and the involvement of three signal transduction pathways in the regulation of PDGF-evoked cell proliferation, migration, and production of VEGF-A was investigated. PDGF stimulated the gene and protein expression of VEGF-A by RPE cells, and increased cell proliferation and chemotaxis. PDGF activated all signaling pathways investigated, as determined by increased phosphorylation levels of ERK1/2, p38, and Akt proteins. The three signaling pathways were involved in the mediation of PDGF-evoked cell proliferation, while p38 and PI3K mediated cell migration, and PI3K mediated secretion of VEGF-A. In addition to VEGF-A, the cells expressed mRNAs for various members of the VEGF family and for their receptors, including VEGF-B, -C, -D, flt-1, and KDR. The data indicate that PDGF selectively stimulates the expression of VEGF-A in RPE cells. PDGF evokes at least three signal transduction pathways which are differentially involved in various cellular responses.
Hollborn
Margrit
M
Department of Ophthalmology and Eye Clinic, University of Leipzig Medical Faculty, 04103 Leipzig, Germany. hollbm@medizin.uni-leipzig.de
Bringmann
Andreas
A
Faude
Frank
F
Wiedemann
Peter
P
Kohen
Leon
L
D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A