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Korol A, Taiyab A, West-Mays JA. RhoA/ROCK signaling regulates TGFβ-induced epithelial-mesenchymal transition of lens epithelial cells through MRTF-A. Mol Med. 2016;22:713-723doi: 10.2119/molmed.2016.00041.
Korol, A., Taiyab, A., & West-Mays, J. A. (2016). RhoA/ROCK signaling regulates TGFβ-induced epithelial-mesenchymal transition of lens epithelial cells through MRTF-A. Molecular medicine (Cambridge, Mass.), 22713-723. https://doi.org/10.2119/molmed.2016.00041
Korol, Anna, et al. "RhoA/ROCK signaling regulates TGFβ-induced epithelial-mesenchymal transition of lens epithelial cells through MRTF-A." Molecular medicine (Cambridge, Mass.) vol. 22 (2016): 713-723. doi: https://doi.org/10.2119/molmed.2016.00041
Korol A, Taiyab A, West-Mays JA. RhoA/ROCK signaling regulates TGFβ-induced epithelial-mesenchymal transition of lens epithelial cells through MRTF-A. Mol Med. 2016 Dec;22:713-723. doi: 10.2119/molmed.2016.00041. Epub 2016 Sep 29. PMID: 27704140; PMCID: PMC5135079.
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Mol Med. 2016 Dec;22:713-723. doi: 10.2119/molmed.2016.00041. Epub 2016 Sep 29.

RhoA/ROCK signaling regulates TGFβ-induced epithelial-mesenchymal transition of lens epithelial cells through MRTF-A.

Molecular medicine (Cambridge, Mass.)

Anna Korol, Aftab Taiyab, Judith A West-Mays

Affiliations

  1. Department of Pathology and Molecular Medicine, McMaster University Health Science Centre, Rm 4H25, 1200 Main St. West. Hamilton, ON, L8N 3Z5, Canada.

PMID: 27704140 PMCID: PMC5135079 DOI: 10.2119/molmed.2016.00041

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.

Keywords: Cataract; beta catenin; cytoskeleton; fibrosis; myofibroblast

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