Abstract
Transforming growth factor (TGF) β2 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 TGFβ2 during EMT in lens epithelial cells (LECs). Importantly, we found TGFβ2 and FGF2 played contrasting roles. Stress fibre formation and up‐regulation of α‐smooth muscle actin (αSMA) induced by TGFβ2 could be reversed by Tpm1/2 knock‐down by siRNA. Expression of Tpm1/2 and stress fibre formation induced by TGFβ2 could be reversed by FGF2. Furthermore, FGF2 delivery to TGFβ‐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 αSMA suppression. However, we found that normal LECs which underwent EMT showed enhanced migration in response to combined TGFβ 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 TGFβs‐driven EMT orchestration may provide clue(s) to develop therapeutic strategies to treat PCO based on Tpm1/2.
Highlights
Age-related cataract, a chronic disorder of ageing, is the main cause of blindness worldwide
To examine whether Mice LECs (MLECs) treated with TGFb or TGFb plus FGF2 showed phenotypic change, we selected TGFb2 as the major isoform expressed in eyes, which plays a role in posterior capsule opacification (PCO) [59], and FGF2 which is a 2016 The Authors
This study provides evidence that Tpm1/2 plays an important role in TGFb2-induced epithelial–mesenchymal transition (EMT), stress fibre formation and cell migration in lens epithelial cells (LECs)
Summary
Age-related cataract, a chronic disorder of ageing, is the main cause of blindness worldwide. PCO is a common, significant complication following cataract surgery. Intraocular lens materials and designs have reduced the PCO rate, but it remains a significant problem worldwide, even in young and infant patients [1, 2]. Aberrant cell growth across the lens capsule often leads to fibrosis and secondary visual loss, known as PCO, so-called secondary or after cataracts [3]. EMT of LECs is the main cause [4,5,6,7]. EMT is related to other eye diseases such as pterygium and glaucoma and the wound healing process after eye surgery [8,9,10].
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