MG53 represses high glucose-induced inflammation and angiogenesis in human retinal endothelial cells by repressing the EGR1/STAT3 axis.

Abstract

BACKGROUND:

Diabetic retinopathy (DR) is a vascular complication of diabetes mellitus that leads to visual injury and blindness. Both angiogenesis and inflammation play an important role in the pathogenesis of DR. Here we aimed to explore the mechanisms of mitsugumin 53 (MG53) in ameliorating the dysfunction induced by high glucose (HG) in humans retinal microvascular endothelial cells (HRECs).

METHODS:

HRECs were subjected to HG in the presence or absence of MG53 overexpression. The effect of MG53 on cell viability and inflammatory response in HG-treated HRECs was measured using the Cell Counting Kit-8 and ELISAs, respectively. Expression of MG53, EGR1, p-STAT3, FGF2, TGFB1, and Angiopoietin-1 in HG-treated HRECs was quantified by western blot or quantitative real-time polymerase chain reaction.

RESULTS:

HG significantly downregulated MG53 in HRECs, which reduced cell viability while inducing angiogenesis and inflammatory response. Upregulation of MG53 reversed these effects of HG. MG53 directly interacted with EGR1 and repressed its expression, which decreased phosphorylation of STAT3 and downregulated FGF2, TGFB1, and Angiopoietin-1. EGR1 up-regulation or STAT3 activation antagonized the protective effects of MG53.

CONCLUSION:

MG53 alleviates HG-induced dysfunction in HRECs by repressing EGR1/STAT3 signaling. Thereby MG53 may have therapeutic potential in DR.

• Authors: Kun-Ming Cui, Zhen-Ping Hu, Ya-Li Wang
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 44 Issue 4 Pg. 484-491 (Aug 2022) ISSN: 1532-2513 [Electronic] England
• PMID: 35438597 (Publication Type: Journal Article)

Chemical References

• Angiopoietin-1
• EGR1 protein, human
• Early Growth Response Protein 1
• STAT3 Transcription Factor
• STAT3 protein, human
• TRIM72 protein, human
• Tripartite Motif Proteins
• Fibroblast Growth Factor 2
• Glucose

Topics

• Angiopoietin-1 (metabolism)
• Cells, Cultured
• Diabetic Retinopathy (drug therapy, metabolism, pathology)
• Early Growth Response Protein 1 (genetics, metabolism)
• Endothelial Cells (metabolism)
• Fibroblast Growth Factor 2 (metabolism)
• Glucose (metabolism, toxicity)
• Humans
• Inflammation (pathology)
• Neovascularization, Pathologic
• STAT3 Transcription Factor (metabolism)
• Tripartite Motif Proteins (genetics, metabolism)