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PC Kothary, E Albeiruti, A Johnson, V Polavarapu, MA DelMonte; Platelet Derived Growth Factor (PDGF) Stimulates Signal Transducer and Activator of Transcription (STAT) Protein Synthesis in Human Retinal Pigment Epithelial Cells (hRPE) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4553.
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Purpose: STAT proteins are a family of transcription factors that mediate the action of several growth factors. The purpose of this study was to assess the effect of PDGF in STAT1 and STAT3 synthesis. Methods: Primary hRPE cell cultures were established from four human eyes obtained from the Michigan Eye Bank. Cells were allowed to grow to confluence and treated with PDGF and genistein. Cell viability was determined by the trypan blue exclusion method. Cell proliferation was monitored by 3H-thymidine (3H-thy) incorporation. 14C-methionine labeled-intracellular STAT1 and STAT3 synthesis was determined by immunoprecipitation using STAT1 and STAT3 antibodies and SDS-PAGE analysis. Data were analyzed by Student 't' test and Wilcoxon Signed Rank test. P<0.05 was considered to be significantly different. Results: PDGF increased hRPE cell number and 3H-thymidine incorporation in a dose dependent manner. PDGF also increased 14C-methionine STAT 1 and STAT 3 protein synthesis in a dose dependent manner. PDGF + genistein inhibited 14C-methionine-PDGF-stimulated STAT1 and STAT 3 protein synthesis compared to PDGF alone (4726±559 vs. 7200±679 and 2195±238 vs. 4738±352, STAT 1 and STAT 3 respectively, CPM±SEM, p<0.05, n=5). SDS-PAGE also showed that PDGF stimulated STAT1 and STAT3 synthesis and genistein blocked it. Conclusion: PDGF is a mitogen for hRPE cells. PDGF stimulates STAT 1 and STAT 3 synthesis via phosphotyrosine kinase signaling pathways in hRPE cells. Our data suggest that activation of STAT1 and STAT3 may be required for PDGF stimulated hRPE cell proliferation and it may play role in proliferative eye diseases.
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