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Rho plays a key role in TGF‐β1‐induced cytoskeletal rearrangement in human retinal pigment epithelium
Author(s) -
Lee Jungeun,
Ko Meekyung,
Joo ChounKi
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21424
Subject(s) - microbiology and biotechnology , stress fiber , rhoa , cytoskeleton , cofilin , rho associated protein kinase , phosphorylation , signal transduction , actin cytoskeleton , biology , actin , transforming growth factor , chemistry , focal adhesion , cell , biochemistry
Proliferative vitroretinopathy (PVR) is caused by retinal pigment epithelial (RPE) cell proliferation and transformation into fibrotic cells that produce extracellular matrix (ECM) components. Transforming growth factor β1 (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 10 ng/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, α‐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. J. Cell. Physiol. 216: 520–526, 2008. © 2008 Wiley‐Liss, Inc.