Transforming growth factor (TGF)-beta 2, gremlin and connective tissue growth factor (CTGF) are known to play important roles in the induction of epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) synthesis. However, the complex functional relationship among gremlin, CTGF and TGF-beta 2 in the induction of EMT and ECM synthesis in human lens epithelial cells (HLECs) has not been reported. In this study, we found that TGF-beta 2, CTGF and gremlin can individually induce the expression of a-smooth muscle actin (alpha-SMA), fibronectin (Fn), collagen type I (COL-I), Smad2 and Smad3 in HLECs. Blockade of CTGF and gremlin effectively inhibited TGF-beta 2-induced expression of alpha-SMA, Fn, COL-I, Smad2, and Smad3 in HLECs. Furthermore blockade of Smad2 and Smad3 effectively inhibited CTGF and gremlin induced expression of alpha-SMA, Fn, COL-I in HLECs. In conclusion, TGF-beta 2, CTGF and gremlin are all involved in EMT and ECM synthesis via activation of Smad signaling pathway in HLECs. Specifically silencing CTGF and gremlin can effectively block the TGF-beta 2-induced EMT, ECM synthesis due to failure in activation of Smad signaling pathway in HLECs. (C) 2014 Elsevier Inc. All rights reserved.