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COL1A1 and SERPINE1 as Potential Therapeutic Targets in Diabetic Retinopathy: A Study Incorporating RNA
Xiaomei Nie1, Gang Su1, Ran Zhang1
1Department of Ophthalmology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, China, zmc.edu.cn.
Background:
Diabetic retinopathy is caused by chronic hyperglycemia, which damages the retina's blood vessels and neurons. This study is aimed at identifying potential therapeutic targets for DR.
Methods:
Transcriptomic and proteomic data were obtained from the Gene Expression Omnibus (GEO) and ProteomeXchange databases, respectively. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were intersected. An enrichment analysis of the overlapping genes was performed based on the DAVID database. A protein-protein interaction (PPI) network (STRING) was analyzed via Cytoscape/cytoHubba to identify key genes. Single-cell RNA-sequencing (scRNA-seq) data were processed using Seurat. Gene set enrichment analysis (GSEA) (clusterProfiler) and molecular docking (EnrichR) were performed. High glucose-induced retinal microvascular endothelial cells (RMECs) were used for functional assays.
Results:
The intersection of DEGs and DEPs yielded shared genes, enriched in the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, complement and coagulation cascades, and ECM-receptor interaction; a PPI network incorporating these genes revealed two key DR-associated highly expressed genes, COL1A1 and SERPINE1. GSEA showed that samples with high expression of these key genes were enriched in pathways such as reactome signaling by TGFB family members, inflammatory response, TGF-β signaling, and reactome cell extracellular matrix interactions. Single-cell and molecular docking analyses revealed high expression of the two key genes in fibroblasts and binding between SERPINE1 and paricalcitol, and HG induction increased their levels in RMECs, whereas knockdown of SERPINE1 repressed RMEC proliferation, migration, and invasion in vitro.
Conclusion:
This study identifies SERPINE1 and COL1A1 as possible DR therapeutic targets, providing new insights into relevant therapeutic development.
Insights
This study identifies SERPINE1 and COL1A1 as key therapeutic targets for diabetic retinopathy (DR). Targeting these genes may offer new treatment strategies for DR by influencing cell proliferation and migration.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genomics
Background:
- Diabetic retinopathy (DR) is a complication of diabetes caused by chronic hyperglycemia.
- Hyperglycemia damages retinal blood vessels and neurons, leading to vision loss.
- Identifying novel therapeutic targets is crucial for effective DR management.
Purpose of the Study:
- To identify potential therapeutic targets for diabetic retinopathy (DR).
- To investigate the molecular mechanisms underlying DR pathogenesis.
- To provide insights for developing new DR treatments.
Main Methods:
- Integrated transcriptomic and proteomic data analysis.
- Identified differentially expressed genes (DEGs) and proteins (DEPs).
- Utilized bioinformatics tools (DAVID, STRING, Cytoscape) and single-cell RNA sequencing (scRNA-seq) for analysis.
Main Results:
- Identified COL1A1 and SERPINE1 as key DR-associated genes.
- Enrichment analysis revealed involvement of PI3K-Akt and AGE-RAGE signaling pathways.
- SERPINE1 knockdown inhibited retinal microvascular endothelial cell (RMEC) proliferation and migration.
Conclusions:
- SERPINE1 and COL1A1 are potential therapeutic targets for DR.
- These findings offer novel insights into DR pathogenesis and treatment development.
- Further research into SERPINE1 and COL1A1 could lead to effective DR therapies.
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