Decorin inhibits glucose-induced lens epithelial cell apoptosis via suppressing p22phox-p38 MAPK signaling pathway

Du, Shanshan; Shao, Jingzhi; Xie, Dandan; Zhang, Fengyan

doi:10.1371/journal.pone.0224251

Cited by 17 publications

(11 citation statements)

References 18 publications

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“…DCN is a member of the SLRP family and is widely located in various connective tissues, serving as a vital regulator in the physiological processes [ 21 ]. Previous study reported that DCN could protect against oxidative stress in glucose-induced lens epithelial cell apoptosis [ 23 ]. In the kidney and neuronal tissues, the administration of DCN intraperitoneally ameliorated the MDA level and increased the SOD level [ 27 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated that autophagy activators such as melatonin and rapamycin showed great potential in AMD treatment [ 18 , 19 ]. Among these activators, decorin (DCN) has been shown to promote autophagy in various cells including endothelial, nucleus pulposus, and breast carcinoma cells [ 20 – 23 ]. DCN, identified as a class I small leucine-rich proteoglycan (SLRP), localizes to the cornea, skin, and other connective tissue and serves as a regulator of various cellular function by fettering to extracellular matrix molecules or through cell receptors [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…A previous study demonstrated that DCN showed an inhibitory effect on oxidative stress and apoptosis in posttraumatic brain injury in rat cerebrum as depicted by increased activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH) [ 27 , 28 ]. Moreover, DCN may inhibit glucose-induced oxidative stress and apoptosis of human lens epithelial cells and protect the barrier function of RPE cells under high-glucose conditions [ 23 ]. However, the potential protective effects of DCN on AMD have not yet been studied.…”

Section: Introductionmentioning

confidence: 99%

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Decorin Protects Retinal Pigment Epithelium Cells from Oxidative Stress and Apoptosis via AMPK-mTOR-Regulated Autophagy

Xie

Cui

et al. 2022

Oxidative Medicine and Cellular Longevity

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Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss among the elderly worldwide with unidentified pathogenesis and limited therapeutic options. Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is central in the development and progression of AMD. Decorin (DCN), a small leucine-rich proteoglycan, possesses powerful antifibrotic, anti-inflammatory, and antiangiogenic properties. DCN has also been reported to serve a cytoprotective role in various cell types, but its protective effects against H2O2-induced oxidative stress and apoptosis in ARPE-19 cells remain unclear. In this study, we showed that DCN significantly attenuated the increase in cell viability loss, apoptosis rate, and reactive oxygen species (ROS) levels in ARPE-19 cells induced by H2O2. Furthermore, DCN activated the AMPK/mTOR pathway to promote autophagy while genetic inhibition of autophagy-related gene 5 (ATG5) hindered autophagic process and diminished the protective role of DCN against oxidative stress in ARPE-19 cells. Collectively, these results suggest that DCN could protect RPE cells from H2O2-induced oxidative stress and apoptosis via autophagy promotion, thus providing the therapeutic potential for AMD prevention and treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Decorin Protects Retinal Pigment Epithelium Cells from Oxidative Stress and Apoptosis via AMPK-mTOR-Regulated Autophagy

Xie

Cui

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The apoptosis of lens epithelial cells is a common cellular basis for the occurrence and development of ARC [23]. A number of common apoptosis pathways such as p53, MAPK, and TGF-β signaling pathways are closely related to the occurrence of ARC, and several appear in our top 20 KEGG pathways [24][25][26]. Some genes of interest in these pathways include DUSP1, ID1, and CAV2, which all function in multiple signaling pathways [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

RNA sequencing and bioinformatics analysis of human lens epithelial cells in age-related cataract

Wang

Su²,

Liu

et al. 2021

BMC Ophthalmol

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Background Age-related cataract (ARC) is the main cause of blindness in older individuals but its specific pathogenic mechanism is unclear. This study aimed to identify differentially expressed genes (DEGs) associated with ARC and to improve our understanding of the disease mechanism. Methods Anterior capsule samples of the human lens were collected from ARC patients and healthy controls and used for RNA sequencing to detect DEGs. Identified DEGs underwent bioinformatics analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Subsequently, reverse transcription quantitative RT-qPCR was used to validate the different expression levels of selected genes. Results A total of 698 up-regulated DEGs and 414 down-regulated DEGs were identified in ARC patients compared with controls by transcriptome analysis. Through GO and KEGG bioinformatics analysis, the functions of significantly DEGs and their possible molecular mechanisms were determined. Sequencing results were verified by RT-qPCR as being accurate and reliable. Conclusions This study identified several genes associated with ARC, which improves our knowledge of the disease mechanism.

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“…Third, in HLEB3 cells, decorin inhibits rac1 expression and p38 MAPK activation under conditions of high-glucose. In a prior study conducted by our lab, we explored the effect of decorin inhibition on the p22 phox -p38 MAPK pathway [23]. Results from that study showed that decorin protect HLEB cells by suppressing the p22phox-p38 MAPK pathway.…”

Section: Discussionmentioning

confidence: 99%

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

Shao¹,

Du²,

Wan³

et al. 2021

IJOVS

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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.

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Decorin inhibits glucose-induced lens epithelial cell apoptosis via suppressing p22phox-p38 MAPK signaling pathway

Cited by 17 publications

References 18 publications

Decorin Protects Retinal Pigment Epithelium Cells from Oxidative Stress and Apoptosis via AMPK-mTOR-Regulated Autophagy

Decorin Protects Retinal Pigment Epithelium Cells from Oxidative Stress and Apoptosis via AMPK-mTOR-Regulated Autophagy

RNA sequencing and bioinformatics analysis of human lens epithelial cells in age-related cataract

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

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