TGFβ promotes Wnt expression during cataract development

TGF beta induces lens epithelial cells to undergo epithelial mesenchymal transition (EMT) and many changes with characteristics of fibrosis including posterior capsular opacification (PCO). Consequently much effort is directed at trying to block the damaging effects of TGF beta in the lens. To do this effectively it is important to know the key signaling pathways regulated by TGF beta that lead to EMT and PCO. Given that Wnt signaling is involved in TGF beta-induced EMT in other systems, this study set out to determine if Wnt signaling has a role in regulating this process in the lens. Using RT-PCR, in situ hybridization and immunolocalization this study clearly shows that Wnts 5a, 5b, 7b, 8a, 8b and their Frizzled receptors are upregulated in association with TGF beta-induced EMT and cataract development. Both rat in vitro and mouse in vivo cataract models show similar profiles for the Wnt and Frizzled mRNAs and proteins that were assessed. Currently it is not clear if the canonical beta-catenin/TCF signaling pathway, or a noncanonical pathway, is activated in this context. Overall, the results from the current study indicate that Wnt signaling is involved in TGF beta-incluced EMT and development of fibrotic plaques in the lens. (C) 2008 Elsevier Ltd. All rights reserved.