Open AccessFGF2 antagonizes aberrant TGFβ regulation of tropomyosin: role for posterior capsule opacity
Author(s) -
Kubo Eri,
Shibata Shinsuke,
Shibata Teppei,
Kiyokawa Etsuko,
Sasaki Hiroshi,
Singh Dhirendra P.
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13030
Subject(s) - microbiology and biotechnology , fibroblast growth factor , transforming growth factor , stress fiber , mapk/erk pathway , actin cytoskeleton , cytoskeleton , actin , epithelial–mesenchymal transition , biology , tropomyosin , myofibroblast , chemistry , cancer research , kinase , signal transduction , focal adhesion , fibrosis , downregulation and upregulation , cell , pathology , medicine , biochemistry , receptor , gene
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 TGF β2 during EMT in lens epithelial cells ( LEC s). Importantly, we found TGF β2 and FGF 2 played contrasting roles. Stress fibre formation and up‐regulation of α‐smooth muscle actin (α SMA ) induced by TGF β2 could be reversed by Tpm1/2 knock‐down by si RNA . Expression of Tpm1/2 and stress fibre formation induced by TGF β2 could be reversed by FGF 2. Furthermore, FGF 2 delivery to TGF β‐treated LEC s perturbed EMT by reactivating the mitogen‐activated protein kinase ( MAPK )/ extracellular signal‐regulated kinase ( ERK ) pathway and subsequently enhanced EMT . Conversely, MEK inhibitor ( PD 98059) abated the FGF 2‐mediated Tpm1/2 and α SMA suppression. However, we found that normal LEC s which underwent EMT showed enhanced migration in response to combined TGF β and FGF 2 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 FGF 2, Tpm1/2 expression and TGF βs‐driven EMT orchestration may provide clue(s) to develop therapeutic strategies to treat PCO based on Tpm1/2.