May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
TGF Beta 1 Induced Cytoskeletal Rearrangement in Human RPE via Rho GTPase-Dependent Pathways
Author Affiliations & Notes
  • J. Lee
    Ophthalmology & Visual Science, The Catholic University of Korea, Seoul, Republic of Korea
  • C.-K. Joo
    Ophthalmology & Visual Science, The Catholic University of Korea, Seoul, Republic of Korea
    Korea Eye Tissue and Gene Bank, Seoul, Republic of Korea
  • Footnotes
    Commercial Relationships  J. Lee, None; C. Joo, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4437. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: retinal pigment epithelium • growth factors/growth factor receptors • proliferative vitreoretinopathy 
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