RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A
Abstract Transforming growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) leads to the formation of ocular fibrotic pathologies, such as anterior subcapsular cataract and posterior capsule opacification. Remodeling of the actin cytoskeleton, mediated by the Rho family of GTPases, p...
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Online Access: | http://link.springer.com/article/10.2119/molmed.2016.00041 |
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doaj-969490869df946c2b52a2978dae97a842020-11-25T02:11:08ZengBMCMolecular Medicine1076-15511528-36582016-09-0122171372310.2119/molmed.2016.00041RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-AAnna Korol0Aftab Taiyab1Judith A West-Mays2Department of Pathology and Molecular Medicine, McMaster University, Health Sciences CentreDepartment of Pathology and Molecular Medicine, McMaster University, Health Sciences CentreDepartment of Pathology and Molecular Medicine, McMaster University, Health Sciences CentreAbstract Transforming growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) leads to the formation of ocular fibrotic pathologies, such as anterior subcapsular cataract and posterior capsule opacification. Remodeling of the actin cytoskeleton, mediated by the Rho family of GTPases, plays a key role in EMT. However, how actin dynamics affect downstream markers of EMT has not been fully determined. Our previous work suggests that myocardin-related transcription factor A (MRTF-A), an actin-binding protein, might be an important mediator of TGFβ-induced EMT in lens epithelial cells. The aim of the current study was to determine the requirement of RhoA/ROCK signaling in mediating TGFβ-induced nuclear accumulation of MRTF-A and ultimate expression of α-smooth muscle actin (αSMA), a marker of a contractile myofibroblast phenotype. Using rat lens epithelial explants, we demonstrate that ROCK inhibition using Y-27632 prevents TGFβ-induced nuclear accumulation of MRTF-A, E-cadherin/β-catenin complex disassembly, and αSMA expression. Using a novel inhibitor specifically targeting MRTF-A signaling, CCG-203971, we further demonstrate the requirement of MRTF-A nuclear localization and activity in the induction of αSMA expression. Overall, our findings suggest that TGFβ-induced cytoskeletal reorganization through RhoA/ROCK/MRTF-A signaling is critical to EMT of lens epithelial cells.http://link.springer.com/article/10.2119/molmed.2016.00041 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Korol Aftab Taiyab Judith A West-Mays |
spellingShingle |
Anna Korol Aftab Taiyab Judith A West-Mays RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A Molecular Medicine |
author_facet |
Anna Korol Aftab Taiyab Judith A West-Mays |
author_sort |
Anna Korol |
title |
RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A |
title_short |
RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A |
title_full |
RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A |
title_fullStr |
RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A |
title_full_unstemmed |
RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A |
title_sort |
rhoa/rock signaling regulates tgfβ-induced epithelial-mesenchymal transition of lens epithelial cells through mrtf-a |
publisher |
BMC |
series |
Molecular Medicine |
issn |
1076-1551 1528-3658 |
publishDate |
2016-09-01 |
description |
Abstract Transforming growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) leads to the formation of ocular fibrotic pathologies, such as anterior subcapsular cataract and posterior capsule opacification. Remodeling of the actin cytoskeleton, mediated by the Rho family of GTPases, plays a key role in EMT. However, how actin dynamics affect downstream markers of EMT has not been fully determined. Our previous work suggests that myocardin-related transcription factor A (MRTF-A), an actin-binding protein, might be an important mediator of TGFβ-induced EMT in lens epithelial cells. The aim of the current study was to determine the requirement of RhoA/ROCK signaling in mediating TGFβ-induced nuclear accumulation of MRTF-A and ultimate expression of α-smooth muscle actin (αSMA), a marker of a contractile myofibroblast phenotype. Using rat lens epithelial explants, we demonstrate that ROCK inhibition using Y-27632 prevents TGFβ-induced nuclear accumulation of MRTF-A, E-cadherin/β-catenin complex disassembly, and αSMA expression. Using a novel inhibitor specifically targeting MRTF-A signaling, CCG-203971, we further demonstrate the requirement of MRTF-A nuclear localization and activity in the induction of αSMA expression. Overall, our findings suggest that TGFβ-induced cytoskeletal reorganization through RhoA/ROCK/MRTF-A signaling is critical to EMT of lens epithelial cells. |
url |
http://link.springer.com/article/10.2119/molmed.2016.00041 |
work_keys_str_mv |
AT annakorol rhoarocksignalingregulatestgfbinducedepithelialmesenchymaltransitionoflensepithelialcellsthroughmrtfa AT aftabtaiyab rhoarocksignalingregulatestgfbinducedepithelialmesenchymaltransitionoflensepithelialcellsthroughmrtfa AT judithawestmays rhoarocksignalingregulatestgfbinducedepithelialmesenchymaltransitionoflensepithelialcellsthroughmrtfa |
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1724916086672982016 |