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S. Horie, S. Sugita, Y. Yamada, M. Mochizuki; Potential Effects of Toll-Like Receptor 4 Signaling on RPE Dedifferentiation by TGFβ. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3814. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferation and dedifferentiation of retinal pigment epithelial (RPE) cells known as epithelial mesenchymal transition (EMT) are associated in pathogenesis in proliferative vitreoretinopathy (PVR). TGFβ is a critical factor to induce RPE-EMT formation. Recently, it is reported that toll-like receptor (TLR) 4 signaling that acts as receptor for lipopolysaccharide (LPS) enhances TGFβ pathway. In this study, we therefore investigated the effect of TLR4 signaling on human RPE treated with TGFβ.
ARPE-19 cell lines were used as human RPE cells, and treated with human recombinant TGFβ2 to induce RPE-EMT formation. The expressions of TLR4, TGFβ receptor (TGFβR), and TGFβ pseudoreceptor (BAMBI) on RPE were analyzed by flow cytometry or RT-PCR. The proliferation of TGFβ-treated RPE stimulated with LPS were assessed by [3H]-thymidine incorporation. Cytokine productions by RPE with LPS stimulation were also measured by cytokine beads array.
RPE-EMT formation was observed morphologically in TGFβ-treated RPE cells. TLR4 was expressed on both RPE and TGFβ-treated RPE, and the expression of TLR4 on the cells was enhanced by LPS stimulation. With stimulus by LPS, cell proliferation and IL-6 production were also enhanced in TGFβ-treated RPE. TGFβ-treated RPE exposed to LPS highly expressed TGFβR. Moreover, BAMBI transcript was downregulated in RPE exposed to LPS.
TLR4 signaling promotes cell proliferation and inflammatory cytokine production of dedifferentiated RPE by TGFβ. Thus, TLR4 enhances TGFβ signaling and RPE dedifferentiation in pathogenic mechanisms of PVR.
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