Role of Smad3 signaling in the epithelial-mesenchymal transition of the lens epithelium following injury

Transforming growth factor-beta (TGF-beta) is important in the development of posterior capsule opacification (PCO), and inhibition of the TGF-beta pathway may represent a novel method of treating PCO. Drosophila protein, mothers against decapentaplegic homolog 3 (Smad3) is a phosphorylated receptor-activated Smad required for the transmission of TGF-beta signals. Smad3 knockout (KO) disturbs the activation of TGF-beta signaling, thus inhibiting the onset of PCO. In the present study, lens epithelial cell (LEC) damage induced by extracapsular cataract extraction was simulated by puncture of the anterior capsule using a 26-gauge hypodermic needle. The effect of Smad3 in the trauma-induced epithelial-mesenchymal transition (EMT) of the lens epithelium in Smad3-KO and wild-type (WT) mice was then observed. The expression levels of EMT markers and extracellular matrix components were measured in the two groups by reverse transcription-quantitative polymerase chain reaction analysis, western blot analysis and immunofluorescence staining. Apoptosis was also detected in the punctured anterior capsule. The Smad3-KO mice exhibited lower expression levels of alpha-smooth muscle actin, lumican, osteopontin, fibronectin and collagen, compared with the WT mice. Additionally, the Smad3-KO mice exhibited a higher percentage of apoptotic cells than the WT mice. Smad3 signaling was associated with the induction of trauma-induced EMT, and Smad3 KO interfered with TGF-beta signaling pathway activation, but did not completely inhibit the trauma-induced EMT in LECs. Therefore, Smad3 may be a target in the treatment of PCO and other fibrosis-related diseases.