Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 MAPK Signaling Pathway

Jingzhi Shao,Shanshan Du,Fengyan Zhang,Jingjing Wan,Lirong Zhang

doi:10.11648/j.ijovs.20210601.11

Abstract

Aim This study was conducted to evaluate the influence of decorin on apoptosis and oxidative stress response upon exposure of human lens epithelial (HLE) cells to high levels of glucose. Methods The HLE cell line (HLEB3) was cultured under various conditions, including normal (5.5 mM) or high glucose (60 mM) medium. Next, 50 nM Decorin was added two hours prior to the addition of high glucose medium. Apoptosis detection was carried out by Western blotting and flow cytometry. Oxidative stress levels were determined by quantifying reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GSH) levels. P38 mitogen-activated protein kinase (MAPK) phosphorylation and rac1 in HLE cells and human lens anterior capsules were evaluated using Western blotting. Knockdown of rac1 and p38 MAPK in HLEB3 cells was achieved using transfection of small-interfering RNAs. Results HLE cells exposed to high levels of glucose underwent oxidative stress and apoptosis, leading to higher proportion of apoptotic cells, ROS generation and a reduction in the bcl/bax ratio, GSH/GSSG ratio, and SOD activity. Additionally, HLEB3 cells exposed to high levels of glucose were found to have increased rac1 and phospho-p38 MAPK. Next, we found that siRNA-mediated knockdown of rac1 or p38 led to a reduction in high-glucose-stimulated cellular apoptosis and oxidative stress. Furthermore, knockdown of rac1 led to a downregulation of p38 MAPK. Interestingly, addition of decorin to HLEB3 cells led to a decrease in apoptosis, oxidative stress, and high-glucose-stimulated induction of rac1 and phospho-p38. Finally, rac1 and p38 levels of capsules were detected to be significantly upregulated in patients with diabetes in comparison to age-matched patients with cataracts. Conclusion The findings indicate that the rac1-p38 pathway plays a role in causing high-glucose-induced injury to the lens epithelial cells. Additionally, these data indicate that decorin can suppress high glucose-stimulated cellular apoptosis and oxidative stress, in part through suppression of the rac1-p38 pathway.

Highlights

Diabetic cataract, which is frequently seen in clinic, is a significant diabetes-associated complication [1]
Studies reported that decorin is able to hinder oxidative stress-related injury and apoptosis in the cerebrum of a Jingzhi Shao et al.: Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 mitogen-activated protein kinase (MAPK) Signaling Pathway post-traumatic brain injuries (TBI) rat model [8, 9]
Our preliminary study showed that decorin inhibits retinal pigment epithelial (RPE) barrier disruption in the context of diabetes by hindering activation of p38 mitogen-activated protein kinase (MAPK) [10]

Summary

Introduction

Diabetic cataract, which is frequently seen in clinic, is a significant diabetes-associated complication [1]. Highglucose-induced oxidative stress is vital to diabetic cataract development. High levels of glucose cause apoptosis, oxidative stress and aggregation of proteins. Apoptosis and oxidative stress tend to occur when human lens epithelial (HLE) cells are incubated with high glucose [3]. Studies reported that decorin is able to hinder oxidative stress-related injury and apoptosis in the cerebrum of a Jingzhi Shao et al.: Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 MAPK Signaling Pathway post-traumatic brain injuries (TBI) rat model [8, 9]. Our preliminary study showed that decorin inhibits retinal pigment epithelial (RPE) barrier disruption in the context of diabetes by hindering activation of p38 mitogen-activated protein kinase (MAPK) [10]. How decorin influences the development of diabetic cataracts remains unclear

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Results

Discussion

Conclusion