FGF2 antagonizes aberrant TGFβ regulation of tropomyosin: role for posterior capsule opacity

Eri Kubo, Shinsuke Shibata, Teppei Shibata, Etsuko Kiyokawa, Hiroshi Sasaki, Dhirendra P. Singh

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)916-928
Number of pages13
JournalJournal of cellular and molecular medicine
Volume21
Issue number5
DOIs
StatePublished - May 1 2017

Keywords

  • FGF2
  • TGFβ2
  • epithelial–mesenchymal transition
  • lens epithelial cells
  • tropomyosin

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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