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ERK1/2-Dependent Gene Expression Contributing to TGFβ-Induced Lens EMT
Magdalena C Wojciechowski1, Daisy Y Shu1,2, Frank J Lovicu1,2
1a Discipline of Anatomy and Histology , Bosch Institute, University of Sydney , Sydney , Australia.
Current Eye Research
|April 14, 2018
Summary
Extracellular signal-regulated kinases 1/2 (ERK1/2) signaling promotes mesenchymal gene expression during transforming growth factor beta (TGFβ)-induced epithelial-to-mesenchymal transition (EMT) in lens cells. ERK1/2 also regulates endogenous lens epithelial genes, impacting normal and pathological processes.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Lens epithelial-to-mesenchymal transition (EMT) is a pathological process implicated in various eye conditions.
- Extracellular signal-regulated kinases 1/2 (ERK1/2) and transforming growth factor beta (TGFβ) signaling pathways are known regulators of cellular processes, including EMT.
Purpose of the Study:
- To identify genes differentially regulated by ERK1/2 signaling during TGFβ-induced EMT in the lens.
- To investigate the role of ERK1/2 in regulating TGFβ-mediated gene expression and its contribution to lens EMT.
Main Methods:
- Rat lens epithelial explants were treated with TGFβ to induce EMT, with or without the ERK1/2 inhibitor UO126.
- Quantitative RT-PCR was used to analyze the expression of genes involved in TGFβ signaling, epithelial markers, cell survival/death, and mesenchymal markers.
- Smad2/3 nuclear immunolabeling confirmed active TGFβ signaling.
Main Results:
- ERK1/2 signaling positively regulated mesenchymal genes (Mmp9, Fn1, Col1a1) and TGFβ-responsive signaling genes (Smad7, Smurf1, Rnf111) during TGFβ-induced EMT.
- UO126 pre-treatment blocked TGFβ-induced Smad2/3 nuclear localization, indicating ERK1/2's role in TGFβ pathway activation.
- TGFβ did not directly impact the expression of examined lens epithelial genes or cell death/survival regulators.
Conclusions:
- TGFβ-mediated ERK1/2 signaling drives mesenchymal gene expression and regulates TGFβ-mediated genes during lens EMT.
- ERK1/2 activity independently influences endogenous lens epithelial gene expression, suggesting a critical role in both normal and pathological lens cell functions.
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