GM3 Interacts with TGFβRs in the Epithelial–Mesenchymal Transition (EMT) During Posterior Capsular Opacification (PCO) Formation

Abstract

Epithelial–mesenchymal transition (EMT) is a scheduled programing and differentiating transition from epithelial phenotype to mesenchymal phenotype. The EMT event is, therefore, the programmed cellular process for differentiation transition from epithelial to mesenchymal type cells. EMT involves in multiple cellular events including development, cataract, wound healing, mobility, tissue fibrosis, and tumor invasion [1, 2]. In lens development, EMT induces the proliferation and transdifferentiation in lens epithelial cells, causing cataract. TGF-β induces EMT. The EMT involves development, cataract, mobility, invasion, wound healing, and tissue fibrosis [1]. Among them, several clinical outcomes including cataract surgery complication, posterior capsular opacification (PCO), and anterior subcapsular cataract (ASC) are accompanied by the known EMT process initiated by lens epithelial cells [2]. The lens epithelial cells are transdifferentiated to mesenchymal-like cells such as myofibroblasts with the phenotypes such as membrane presence of fibronectin, type 1 collagen, and α-smooth muscle actin (SMA) [2, 3]. PCO is frequently caused by the EMT process in lens epithelial cells through mesenchymal-like transdifferentiation of myofibroblasts and expression of the SMA, extracellular type 1 collagen, and fibronectin in ocular tissues. Lens epithelial cells-mediated PCO event is promoted by certain growth factors including EGF, FGF, HGF, and TGF-β [4–7]. The TGF-β signaling involves several biochemical processes such as the TGFβ/Smads signaling pathway. As a factor of scleroderma and tissue fibrosis, TGF-β induces EMT event and extracellular matrix (ECM) production with expression of type 1 collagen and fibronectin in ocular tissues [1, 7]. Upon TGF-β treatment, TGF-β internalizes the target cells through phosphorylation of Ser/Thr residues present on TGF-β receptor I (TGFβRI) after pairing with TGFβRI and TGFβRII. The phosphorylated TGFβRI activates receptor-activated Smad2/Smad3 (R-Smad) [8]. The activated Smad2/Smad3 binds to the central mediator named Smad4 and translocates to the nucleus region. Smad complex induces EMT-related multifunctional gene [9]. TGF-β-related Smad also involves EMT-induced human lens epithelial (HLE) [10]. During the posterior capsular and anterior polar cataracts, TGF-β essentially act for EMT event, changes in cellular phenotype and production of ECM, which contains the type 1 collagen and fibronectin via new synthesis in ocular tissues [1, 2].