1. Downregulation of OPA3 is responsible for transforming growth factor-β-induced mitochondrial elongation and F-actin rearrangement in retinal pigment epithelial ARPE-19 cells.
- Author
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Ryu SW, Yoon J, Yim N, Choi K, and Choi C
- Subjects
- Actins genetics, Actins metabolism, Antigens, CD genetics, Antigens, CD metabolism, Cadherins agonists, Cadherins genetics, Cadherins metabolism, Cell Line, Cell Movement drug effects, Dynamins, Epithelial Cells cytology, Epithelial Cells metabolism, Epithelial-Mesenchymal Transition genetics, GTP Phosphohydrolases antagonists & inhibitors, GTP Phosphohydrolases genetics, GTP Phosphohydrolases metabolism, Humans, Microtubule-Associated Proteins antagonists & inhibitors, Microtubule-Associated Proteins genetics, Microtubule-Associated Proteins metabolism, Mitochondria drug effects, Mitochondrial Membrane Transport Proteins antagonists & inhibitors, Mitochondrial Membrane Transport Proteins genetics, Mitochondrial Membrane Transport Proteins metabolism, Mitochondrial Proteins antagonists & inhibitors, Mitochondrial Proteins genetics, Mitochondrial Proteins metabolism, Organelle Shape drug effects, Proteins antagonists & inhibitors, Proteins metabolism, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Retinal Pigment Epithelium cytology, Retinal Pigment Epithelium metabolism, Signal Transduction, Smad2 Protein antagonists & inhibitors, Smad2 Protein genetics, Smad2 Protein metabolism, Transforming Growth Factor beta pharmacology, Vimentin agonists, Vimentin genetics, Vimentin metabolism, Actins chemistry, Epithelial Cells drug effects, Epithelial-Mesenchymal Transition drug effects, Gene Expression Regulation drug effects, Proteins genetics, Retinal Pigment Epithelium drug effects
- Abstract
Transforming growth factor-β signaling is known to be a key signaling pathway in the induction of epithelial-mesenchymal transition. However, the mechanism of TGF-β signaling in the modulation of EMT remains unclear. In this study, we found that TGF-β treatment resulted in elongation of mitochondria accompanied by induction of N-cadherin, vimentin, and F-actin in retinal pigment epithelial cells. Moreover, OPA3, which plays a crucial role in mitochondrial dynamics, was downregulated following TGF-β treatment. Suppression of TGF-β signaling using Smad2 siRNA prevented loss of OPA3 induced by TGF-β. Knockdown of OPA3 by siRNA and inducible shRNA significantly increased stress fiber levels, cell length, cell migration and mitochondrial elongation. In contrast, forced expression of OPA3 in ARPE-19 cells inhibited F-actin rearrangement and induced mitochondrial fragmentation. We also showed that Drp1 depletion increased cell length and induced rearrangement of F-actin. Depletion of Mfn1 blocked the increase in cell length during TGF-β-mediated EMT. These results collectively substantiate the involvement of mitochondrial dynamics in TGF-β-induced EMT.
- Published
- 2013
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