Sprouty2 Suppresses Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells through Blockade of Smad2 and ERK1/2 Pathways

Abstract

Transforming growth factor β (TGFβ)-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) plays a key role in the pathogenesis of anterior subcapsular cataract (ASC) and capsule opacification. In mouse lens, Sprouty2 (Spry2) has a negative regulatory role on TGFβ signaling. However, the regulation of Spry2 during ASC development and how Spry2 modulates TGFβ signaling pathway in human LECs have not been characterized. Here, we demonstrate that Spry2 expression level is decreased in anterior capsule LECs of ASC patients. Spry2 negatively regulates TGFβ2-induced EMT and migration of LECs through inhibition of Smad2 and ERK1/2 phosphorylation. Also, blockade of Smad2 or ERK1/2 activation suppresses EMT caused by Spry2 downregulation. Collectively, our results for the first time show in human LECs that Spry2 has an inhibitory role in TGFβ signaling pathway. Our findings in human lens tissue and epithelial cells suggest that Spry2 may become a novel therapeutic target for the prevention and treatment of ASC and capsule opacification.

Killing two birds with one stone: dual blockade of integrin and FGF signaling through targeting syndecan-4 in postoperative capsular opacification

“… 37 We next tested whether downregulation of SDC-4 also abrogated the migratory effects of FGF on LECs by the wound healing assay. 26 We found that bFGF significantly increased LEC migration, which could be suppressed by SDC-4 KD ( Figures 3a and b ). In addition, the transwell assay showed that SDC-4 KD significantly suppressed cell migration towards the FGF-containing medium ( Figures 3c and d ).…”

“…To determine the role of SDC-4 in FGF signaling, we knocked down SDC-4 in LECs by using RNAi as previously described. 26 We observed a significant downregulation of SDC-4 after SDC-4 siRNA transfection at both transcript and protein levels ( Supplementary Figure 1 ). Then, we performed a CCK-8 assay to evaluate cell proliferation.…”

“…Although ASC and postoperative capsular opacification are regarded as two different types of cataracts, they share common molecular and cellular mechanisms, and both are regulated by the FGF and integrin signaling pathways. 26 , 27 , 45 , 46 , 47 First, we analyzed the expression level of SDC-4 before and after injury by real-time PCR. We found that the expression level of SDC-4 was significantly upregulated at 1 day, 3 days, and 7 days after injury ( Figure 6b ), which is consistent with previous findings that SDC-4 is upregulated during wound healing.…”

Improvement of Uveal and Capsular Biocompatibility of Hydrophobic Acrylic Intraocular Lens by Surface Grafting with 2-Methacryloyloxyethyl Phosphorylcholine-Methacrylic Acid Copolymer

“…Formation of ACO includes two stages: an early stage of LEC proliferation and a late stage involving EMT and ECM production. The LEC proliferation process is regulated by various cytokines and growth factors, such as IL-1, IL-6, transforming growth factor (TGF) and fibroblast growth factor (FGF), which are secreted by residual LECs and inflammatory cells424344. Hydrophobic IOL has a higher incidence rate of ACO than hydrophilic IOL, because hydrophobic surfaces tend to attract more remnant LECs and inflammatory cells to adhere and proliferate5645.…”

The role of focal adhesion kinase in transforming growth factor-β2 induced migration of human lens epithelial cells

“…A variety of structural and signaling proteins have been demonstrated to facilitate PCO development: Transforming growth factor (TGF)-β expression is increased in response to injury (3) and it has been demonstrated that TGF-β not only induces epithelial-to-mesenchymal transition (EMT) in LECs, but also regulates cell migration, which are each considered key events in the initiation of PCO (4). In addition to the canonical Mothers against decapentaplegic signaling pathway, which mediates essential functions of TGF-β, non-canonical signaling pathways also exist and are involved in cell type-or process-specific events (5).…”