Heat stress regulates the migration and proliferation of lens epithelial cells through ferroptosis and NCOA4-FTH1 interaction

Lei Lin; Lili Liang; Liming Xu; Yu Zheng; Hanwen Guo; Bei Zhang; Yun-E Zhao

doi:10.1016/j.exer.2024.110182

Heat stress regulates the migration and proliferation of lens epithelial cells through ferroptosis and NCOA4-FTH1 interaction

Exp Eye Res. 2024 Nov 23:251:110182. doi: 10.1016/j.exer.2024.110182. Online ahead of print.

Authors

Lei Lin¹, Lili Liang¹, Liming Xu¹, Yu Zheng¹, Hanwen Guo¹, Bei Zhang¹, Yun-E Zhao²

Affiliations

¹ National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
² National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China. Electronic address: zye@mail.eye.ac.cn.

PMID: 39586514
DOI: 10.1016/j.exer.2024.110182

Abstract

Posterior capsule opacification (PCO) due to the proliferation and migration of lens epithelial cells (LECs) is the main complication after surgery. Heat stress has demonstrated impressive results in halting cell proliferation and migration, while also facilitating cell death. This study aimed to investigate the role and mechanism of ferroptosis in the proliferation and migration of LECs under heat stress. CCK-8 assays, scratch assays, and transcriptome analysis were used to evaluate the impact of temperature on human lens epithelial cells (HLECs) and explore the potential mechanisms. The role of ferroptosis in the proliferation of HLECs induced by heat was investigated using the ferroptosis inhibitor Fer-1 and siRNA-mediated NCOA4 protein interference. Fluorescence staining and Western blot experiments were used to detect the expression of Fe²⁺, reactive oxygen species (ROS), and ferroptosis-related proteins NCOA4, FTH1, and SLC3A2. The results of CCK-8 assays, scratch assays, and transcriptome analysis demonstrated significant thermal effects on HLEC behavior. After heat treatment, there were significant changes in the fluorescence expression of Fe²⁺ and ROS in the HLECs and lens explant. In addition, the expression of NCOA4, FTH1, and SLC3A2 also changed significantly. Using Fer-1 or NCOA4 siRNA-mediated interference restored cell viability decreased by thermal stress. Furthermore, interference with NCOA4 protein effectively restored the expression of Fe²⁺, ROS, and FTH1. In conclusion, heat stress has a significant effect on LECs by regulating ferroptosis and the interaction between NCOA4 and FTH1 proteins play an important role.

Keywords: Ferroptosis; Heat stress; Lens epithelial cell; NCOA4.