Lenticular cytoprotection, part 2: link between glycogen synthase kinase-3β, epithelial to mesenchymal transition, and mitochondrial depolarization.

摘要: Purpose: The inhibition of GSK-3β blocks mitochondrial membrane permeability transition (mMPT) for HLE-B3 cells in atmospheric oxygen. GSK-3β, as part a multifactorial complex, also regulates nuclear levels β-catenin, known coordinator cell survival and adhesion. purpose these studies was to demonstrate novel, but likely disadvantageous, link between β-catenin’s influence on the expression pro-survival protein, vascular endothelial growth factor (VEGF), resulting enhanced lens epithelial protection against depolarization β-catenin an inducer mesenchymal (EMT). Methods: Virally transformed human (HLE-B3) were treated with SB216763, specific inhibitor catalytic activity XAV939, that bars translocation from cytoplasm nucleus. Western blot analysis employed detect cytoplasmic phospho-β-catenin, pBcl-2 EMT proteins, α-smooth muscle actin (α-SMA), fibronectin. ELISA used measure VEGF culture supernatants. JC-1 performed analyze either SB216763 or XAV939 depolarization. Results: Cultured maintained hypoxia (1% oxygen) subsequently reintroduced into oxygen illustrated marked phosphorylation glycogen synthase (downstream substrate GSK-3β) significant increase β-catenin. augmented positively correlated increased α-SMA fibronectin, both marker proteins indicative EMT. elicited expression, resistance Treatment resulted decreased levels, pBcl-2, well Conclusions: data support model whereby onset may circuitously benefit synthesis by setting up potentially harmful situation mesen chymal population be more resistant than which it originated. These findings potential therapeutic relevance developing strategies undermine progression normal without subverting viability.