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

Transforming growth factor-β (TGF-β) is important in the development of posterior capsule opacification (PCO), and inhibition of the TGF-β 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-β signals. Smad3 knockout (KO) disturbs the activation of TGF-β 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 α-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-β 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.