Role of Osmotic Response Element-Binding Protein in High Glucose-Induced Cataractogenesis: Involvement of ERK and p38 MAPK Pathways

Kun He; Binxin Pan; Pengfei Tian; Guoning Ye

doi:10.2174/0118743641311706240722091620

What is it about?

This study explores the role of a specific protein, Osmotic Response Element-Binding Protein (OREBP), in the development of cataracts caused by high glucose levels, such as in diabetic conditions. The researchers found that when lens cells are exposed to high glucose, the OREBP protein increases in response to the stress, which is part of a cascade of events leading to cataract formation. By understanding how this protein is regulated, particularly through certain signaling pathways, the study provides insight into potential therapeutic targets for preventing or treating diabetic cataracts. The findings are significant for better understanding how diabetes contributes to eye diseases and offer directions for future research in finding treatments for diabetic cataracts.

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Why is it important?

This study is important because it uncovers the molecular mechanisms behind diabetic cataracts, which are a major cause of vision impairment in diabetic patients. By focusing on Osmotic Response Element-Binding Protein (OREBP), the research highlights its role in high glucose-induced cataractogenesis. This is the first study to directly connect OREBP with the ERK and p38 MAPK signaling pathways in lens cells under high glucose conditions. The findings suggest that OREBP plays a significant role in regulating osmotic pressure in the lens, and its dysregulation could be a key factor in cataract formation. Understanding these pathways opens new avenues for targeted therapies to prevent or treat cataracts in diabetic patients, potentially improving the quality of life for millions of people affected by diabetes worldwide.

Perspectives

Working on this study was particularly rewarding because it addressed a significant gap in our understanding of diabetic cataractogenesis, specifically the role of OREBP under high glucose conditions. It was exciting to uncover the molecular details of how this protein responds to osmotic stress, a mechanism that has been largely unexplored in the context of cataract formation. This research provides a new perspective on the intersection of molecular stress responses and eye health, potentially paving the way for targeted therapies for diabetic cataracts. I believe this study not only contributes to ophthalmic research but could also inspire broader explorations into osmotic stress across other disease models. I look forward to seeing how these findings can influence future treatments and the potential collaborations this might spark with other research areas, especially in diabetic complications.
Kun He

This page is a summary of: Role of Osmotic Response Element-Binding Protein in High Glucose-Induced Cataractogenesis: Involvement of ERK and p38 MAPK Pathways, The Open Ophthalmology Journal, July 2024, Bentham Science Publishers,
DOI: 10.2174/0118743641311706240722091620.
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Role of Osmotic Response Element-Binding Protein in High Glucose-Induced Cataractogenesis: Involvement of ERK and p38 MAPK Pathways
Abstract: Background: Osmotic Response Element-binding Protein (OREBP) is a key regulator in cellular responses to osmotic stress. However, its specific role in cataractogenesis remains unclear. This study aimed to investigate the mechanisms regulating OREBP expression in high-glucose environments and examine the associated signaling pathways. Methods: Human Lens Epithelial Cells (HLEpiCs) were cultured and treated with normal (25 mmol/L) and high (300 mmol/L) concentrations of D-glucose. To assess the cellular response, western blot analysis was performed to detect the activation of ERK/p38MAPKs in HLEpiCs. The mRNA and protein expression levels of OREBP were measured using RT-PCR and western blot techniques, respectively. Specific inhibitors for ERK (U0126) and p38 MAPK (SB239063) were applied to assess their roles in OREBP expression. Additionally, OREBP expression was examined in the lens subcapsular epithelium of diabetic patients and rats using RT-PCR and immunofluorescence techniques. Results: Following exposure to varying glucose concentrations, OREBP mRNA levels in HLEpiCs peaked at 4 hours with 300 mM glucose, showing significant upregulation at 2 and 4 hours. Western blot analysis revealed a corresponding increase in OREBP protein levels after 24 hours of high glucose exposure. Morphologically, HLEpiCs exhibited compact growth and increased apoptosis under high glucose conditions, contrasting with their initial polygonal morphology. OREBP expression was markedly elevated in the lens subcapsular epithelium of diabetic patients and rats, correlating with high glucose stress. Furthermore, phosphorylation of ERK and p38 MAPK proteins was significantly induced within 45 minutes of exposure to 300 mM glucose. Inhibition experiments using ERK inhibitor U0126 and p38 MAPK inhibitor SB239063 demonstrated substantial downregulation of OREBP mRNA expression. Combination treatment with both inhibitors consistently suppressed OREBP protein expression after 24 hours of high glucose exposure. Conclusion: In summary, our study reveals that OREBP is upregulated in response to high glucose levels through the activation of ERK and p38 MAPK pathways. These findings provide valuable insights into the molecular mechanisms of cellular responses to osmotic stress in high-glucose environments, offering potential therapeutic targets for diabetic cataracts. Future research should explore the specific functions of OREBP in cataractogenesis and its potential as a therapeutic target. Keywords: Osmotic response element bi

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Kun He

Role of Osmotic Response Element-Binding Protein in High Glucose-Induced Cataractogenesis: Involvement of ERK and p38 MAPK Pathways

What is it about?

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