The Exploration Of Senescent And Apoptotic Mechanisms In Human Lens Epithelial Cells By Importin α3 Protein

As ARC(age-related cataract)is a complex disorder caused by multiple risk factors,it is wise to investigate these factors and study mechanisms of the disease in order to design strategies for treatment and prevention.In the former work,we have successfully conducted a genome-wide association study(GWAS)analysis of ARC and identified KPNA4 as the new susceptibility gene for ARC.Here,we do effort to investigate the function of KPNA4 and its epigenetic regulation.With the model of senescent and apoptotic human lens epithelial cells in vitro,we confirmed the role of importin a3 in lens aging by using the methods of cell immunofluorescence,Western-Blot,overexpressive plasmid vector.Our results detected importin a3 improving p53 and then flicking signal pathway apoptosis regulators.This reveal the mechanism of cell senescence and apoptosis induced by importin α3 and further improve our understanding of the molecular mechanism underlying lens opacity.And using KPNA4 knock out zebrafish,we find many abnormal protein aggregated in the lens central area,also the number and volume of mitochondria increased,by immunohistochemistry and transmission electron microscopy technology,which prove KPNA4 is significant to development of cataract.It provides a powerful theory for the further study of the mechanism of importin a3,and a better direction for future research on the pathogenesis of age-related cataract.