Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 21, Issue 5, Pages 916-928Publisher
WILEY
DOI: 10.1111/jcmm.13030
Keywords
epithelial-mesenchymal transition; tropomyosin; lens epithelial cells; FGF2; TGF beta 2
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Funding
- Japan Society for the Promotion of Science (JSPS) [JP23592588]
- National Eye Institute, National Institute of Health (NIH) [EY024589]
- Research for Preventing Blindness
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Transforming growth factor (TGF) beta 2 and fibroblast growth factor (FGF) 2 are involved in regulation of posterior capsule opacification (PCO) and other processes of epithelial-mesenchymal transition (EMT) such as cancer progression, wound healing and tissue fibrosis as well as normal embryonic development. We previously used an in vivo rodent PCO model to show the expression of tropomyosin (Tpm) 1/2 was aberrantly up-regulated in remodelling the actin cytoskeleton during EMT. In this in vitro study, we show the Tpms family of cytoskeleton proteins are involved in regulating and stabilizing actin microfilaments (F-actin) and are induced by TGF beta 2 during EMT in lens epithelial cells (LECs). Importantly, we found TGF beta 2 and FGF2 played contrasting roles. Stress fibre formation and up-regulation of alpha-smooth muscle actin (alpha SMA) induced by TGF beta 2 could be reversed by Tpm1/2 knock-down by siRNA. Expression of Tpm1/2 and stress fibre formation induced by TGF beta 2 could be reversed by FGF2. Furthermore, FGF2 delivery to TGFb-treated LECs perturbed EMT by reactivating the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and subsequently enhanced EMT. Conversely, MEK inhibitor (PD98059) abated the FGF2-mediated Tpm1/2 and aSMA suppression. However, we found that normal LECs which underwent EMT showed enhanced migration in response to combined TGF beta and FGF2 stimulation. These findings may help clarify the mechanism reprogramming the actin cytoskeleton during morphogenetic EMT cell proliferation and fibre regeneration in PCO. We propose that understanding the physiological link between levels of FGF2, Tpm1/2 expression and TGF beta s-driven EMT orchestration may provide clue(s) to develop therapeutic strategies to treat PCO based on Tpm1/2.
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