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Teppei Shibata, Shinsuke Shibata, Naoko Shibata, Etsuko Kiyokawa, Hiroshi Sasaki, Dhirendra P Singh, Eri Kubo; FGF-2 regression of the tropomyosin expression through MAPK/ERK kinase pathway in lens epithelial cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2629.
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FGF2 and TGFβ2 families are known to play a crucial role in regulating PCO formation after cataract surgery. The involvement of tropomyosin (Tpm) family is implicated in the epithelial-mesenchymal transition (EMT) and epithelial-myofibroblastic transition (EMyoT) in the posterior capsule opacification (PCO) process. Previously we demonstrated that cotreatment of FGF-2 and TGF-β2 promotes the EMyoT with TGF-β2-mediated induction of Tpm1α/2β and αSMA. In this study, we examined the effects of FGF2-mediated MAPK/ERK signaling on TGF-β2-induced EMT.
Primary mouse lens epithelial cells (mLECs) growing in DMEM containing 0.5% bovine serum albumin were treated with 0 to 10ng/ml of FGF-2 and/or TGFβ-2 with or without FGF inhibitor (SU5402) and Erk-MEK pathway inhibitor(s) (PD98059). Amounts of Tpm, Erk and pErk were examined using Western blot analysis with their corresponding specific antibodies. In a similar culture condition, cell migration assay and cell contraction assay were performed using these mLECs.
pErk was increased in mLECs treated with FGF2for 1 hour, while levels of Tpm1α/2β and αSMA protein were markedly decreased in these cells. However, co-treatment of FGF inhibitor (SU5402) and Erk-MEK pathway inhibitor (PD98059) inhibited the MAPK/ERK signaling as well as the reduced expression of Tpm1α/2β and αSMA. FGF2 and TGF-β2-mediated induction of cell migration and cell contraction were inhibited by the addition of PD98059.
Collectively, results revealed involvement of FGF2-MAPK pathway in FGF2-mediated inhibition of Tpm expression. The study demonstrated the use of Erk-MEK pathway inhibitor to reverse TGF-β2- and FGF2-induced EMT and cell migration and block the PCO process.
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