Expression of PDGF and their receptors in human retinal pigment epithelial cells and fibroblasts: regulation by TGF-beta.
Platelet derived growth factors (PDGF) are known to be associated with vitreoretinal disorders such as proliferative vitreoretinopathy (PVR). We have studied the expression of PDGF and their receptors in human retinal pigment epithelial cells (HRPE) and choroid fibroblasts (HCHF), and the regulation of PDGF and its receptors by various cytokines and growth factors. RT-PCR analyses showed enhanced expression of PDGF-A and PDGF-B mRNA in HRPE treated with TGF-beta, but not with other cytokines. A minimal increase was observed in PDGF-A mRNA in TGF-beta treated HCHF cells. PDGF-R alpha mRNA, which was expressed prominently in HCHF and at very low levels in HRPE, was not affected by any of the agents. PDGF-R beta was not detectable in either HRPE or HCHF. HRPE secreted PDGF-AA and AB constitutively, and this secretion was significantly enhanced by TGF-beta. In contrast, HCHF cultures did not secrete detectable levels of any of the three isoforms of PDGF (AA, AB, BB). All three human recombinant PDGF isoforms enhanced HCHF cell proliferation significantly, while only a minimal increase was observed in HRPE. PDGF isoforms also induced HCHF cell elongation and promoted migration of HCHF in an in vitro wound assay. The results presented in this study demonstrate that TGF-beta activated RPE cells produce PDGF that may act on fibroblasts and other mesenchyme derived cells which express PDGF receptors. These studies indicate that the promotion of the proliferation and migration of mesenchymal cells by RPE cell derived PDGF may facilitate the formation of fibrovascular tissues associated with PVR.
Nagineni
Chandrasekharam N
CN
Laboratory of Immunololgy, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kutty
Veena
V
Detrick
Barbara
B
Hooks
John J
JJ
D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002829:Choroid / Q000166:cytology / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A; C095477:platelet-derived growth factor AB; D000077214:Becaplermin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta