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29-01-2025 | Cataract | Basic Science

FoxO1 promotes high glucose-induced inflammation and cataract formation via JAK1/STAT1

Authors: Yike Li, An-Peng Pan, Yishan Ye, Xu Shao, Ruixue Tu, Yang Liu, A-Yong Yu

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology

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Abstract

Purpose

To investigate whether in diabetic cataract (DC), FoxO1 regulates high glucose (HG)-induced activation of NLRC4/IL-6 inflammatory mediators in human lens epithelial cells (SRA01/04) via the JAK1/STAT1 pathway, leading to cataract formation.

Methods

Expression levels of FoxO1, inflammatory factor IL-6 and inflammatory vesicle NLRC4 were examined in SRA01/04 under high glucose (HG) stress at 25–150 mM. Rat lenses were also cultured using HG medium with or without the addition of the FoxO1 inhibitor AS1842856 and the JAK1 agonist RO8191. 5.5 mM glucose concentration group (NG) was used as a control. Real-time PCR, Western blots, and immunofluorescent staining evaluated the mRNA and protein levels of FoxO1, NLRC4, and IL-6. Apoptosis, cell viability, and EDU Staining were also assessed.

Results

HG stimulation induced elevated FoxO1 expression and caused NLRC4/IL-6 activation in a concentration-dependent manner. Whereas knockdown of FoxO1 inhibited the high expression of NLRC4/IL-6 inflammatory mediators in response to HG stimulation. The growth of SRA01/04 was inhibited under HG condition, and the cell proliferation ability was restored and even promoted by knocking out FoxO1. HG incubation of rat lens resulted in lens clouding and cataract formation, which was prevented by AS1842856 treatment and reversed by RO8191.

Conclusion

FoxO1 positively regulates HG-induced SRA01/04 inflammatory activation through the JAK1/STAT1 pathway and promotes DC. This provides a feasible strategy for the treatment of diabetic cataract.
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Metadata
Title
FoxO1 promotes high glucose-induced inflammation and cataract formation via JAK1/STAT1
Authors
Yike Li
An-Peng Pan
Yishan Ye
Xu Shao
Ruixue Tu
Yang Liu
A-Yong Yu
Publication date
29-01-2025
Publisher
Springer Berlin Heidelberg
Keyword
Cataract
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-025-06744-6