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Q. Bian, A. F. Fernandes, P. Pereira, A. Taylor, F. Shang; The Expression of Complement Factor H (CFH) and Factor B (CFB) in RPE Is Controlled by the Ubiquitin-Proteasome Pathway (UPP). Invest. Ophthalmol. Vis. Sci. 2007;48(13):3048.
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Emerging evidences suggest that inappropriate activation of complement via the alternative pathway is closely related to age-related macular degeneration (AMD). CFH is a negative regulator and CFB is a positive regulator of the alternative pathway of complement activation. The UPP plays important roles in regulating signal transduction and gene expression. The objective of this study is to investigate the effect of impairment of the UPP on expression and secretion of CFH and CFB by RPE cells.
The proteasome in ARPE-19 cells was inhibited by MG132 or epoxomicin. CFH and CFB expression in ARPE-19 cells was studied by quantitative RT-PCR and secretion of CFH was determined by ELISA assays.
ARPE-19 cells express high levels of CFH and CFB. Inhibition of the proteasome decreased the expression and secretion of CFH by 80%. In contrast, the expression of CFB only decreased by 30%%. In addition, expression of CFH was stimulated by interferon gamma. Even in the presence of interferon gamma, the expression and secretion of CFH was still reduced by proteasome inhibitors.
The expression and secretion of CFH and CFB in RPE is under the control of the UPP. Inhibition of the UPP in RPE down-regulates both CFH and CFB, but the CFH was preferentially affected. These data indicate that aging- or stress-related impairment of the UPP may play a role for the inappropriate activation of complement via the alternative pathway and the pathogenesis of AMD.
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