Curcumin Restrains TGF-β2-Induced Proliferation, Migration, Invasion and EMT in Lens Epithelial Cells by Regulating FGF7/ZEB1 Axis

Abstract

Posterior capsular opacification (PCO) is the most common complication after cataract surgery characterized by hyperproliferation, migration and epithelial-mesenchymal transition (EMT) in residual lens epithelial cells (LECs). Curcumin is a polyphenol compound possessing diverse pharmacological properties. Here, we investigated the functions and its potential mechanisms of curcumin in PCO using transforming growth factor beta2 (TGF-β2)-treated LECs. Cell phenotypes were analyzed using MTT, 5-thynyl-2′-deoxyuridine (EdU), transwell, and scratch assays, respectively. Levels of FGF7 (Fibroblast Growth Factor 7), ZEB1 (Zinc finger E-box binding homeobox 1), and EMT-related proteins were detected by qRT-PCR and western blot analysis. The protein interaction between FGF7 and ZEB1 was validated using Co-immunoprecipitation assay. Curcumin treatment weakened TGF-β2-induced proliferation, migration, invasion and EMT progression in LECs. The expression of FGF7 was boosted by curcumin in LECs. Functionally, FGF7 deficiency suppressed TGF-β2-induced proliferation, migration, invasion and EMT progression in LECs, and could reverse the suppressing action of curcumin on TGF-β2-induced LEC dysfunction. Mechanistically, FGF7 directly interacted with ZEB1, and curcumin could regulate ZEB1 expression via FGF7. Moreover, ZEB1 overexpression could abolish the protective effects of curcumin or FGF7 deficiency on LECs under TGF-β2 stimulation. In conclusion, curcumin protected LECs against TGF-β2-induced enhancement on the proliferation, migration, invasion and EMT process by regulating FGF7/ZEB1 axis, suggesting a new insight into the application of curcumin in PCO therapy.