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J. Lee, C.-K. Joo; TGF Beta 1 Induced Cytoskeletal Rearrangement in Human RPE via Rho GTPase-Dependent Pathways. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4437.
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Proliferative vitroretinopathy (PVR) is caused by retinal pigment epithelial (RPE) cell proliferation and transformation into fibrotic cells that produce extracellular matrix (ECM) components. TGF-β1 is known to play an important role in PVR pathogenesis. To determine how TGF-β1 mediates the pathogenic changes in RPE cells, we characterized the effects of TGF-β1 on the morphology, ECM accumulation, and stress fiber formation of ARPE-19 cells, a human RPE cell line. We then elucidated the signaling pathways that mediate these effects.
Serum-starved ARPE-19 cells were incubated with vehicle alone or 10ng/ml TGF-β1 and their morphological changes were examined by phase-contrast microscopy. Actin reorganization was examined by immunochemistry and confocal microscopy. Protein phosphorylation was analyzed by Western blot analysis.
TGF-β1 treatment induced cytoskeleton reorganization, a-SMA expression, increased the phosphorylation of ERK, Smad2/3, and AKT, and activated RhoA and Rac1.Cytoskeletal rearrangement was prevented by pretreatment with a Rho inhibitor and by expression of a dominant negative form of Rho. TGF-β1 also increased LIM kinase and cofilin phosphorylation and the Rho inhibitor blocked this effect.
We propose that TGF-β1 induces human RPE cells to undergo cytoskeletal actin rearrangement via Rho GTPase-dependent pathways that modulate LIM kinase and cofilin activity. This inhibits actin depolymerization and induces the cytoskeletal rearrangements in RPE cells that result in the characteristic features of PVR.
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