The contribution of adiponectin to diabetic retinopathy progression: Association with the AGEs-RAGE pathway

• Published in: Heliyon Vol. 10; no. 17; p. e36111
• Main Authors: Fu, Min, Zhengran, Li, Yingli, Li, Tong, Wu, Liyang, Cai, Xi, Guo, Xiongyi, Yang, Mingzhe, Cao, Guoguo, Yi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.09.2024; Elsevier
• Subjects: Adiponectin; Advanced glycation end products; Diabetic retinopathy; ELISA; Eye; Genomics; Glucose; Inflammation; Single-cell RNA sequencing; Eye; Diabetic retinopathy; Advanced glycation end products; Single-cell RNA sequencing; Genomics; Inflammation; Glucose; Adiponectin; ELISA
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e36111

Diabetic retinopathy (DR) is a chronic complication of diabetes. Given that adiponectin plays a key role in DR progression, this study aims to elucidate the molecular mechanisms of sDR progression related to adiponectin. First, we extracted the microarray dataset GSE60436 from the Gene Expression Omnibus (GEO) database to identify hub genes associated with DR. Pathway enrichment analysis revealed a focus on inflammation, oxidative stress, and metabolic disease pathways. Gene Set Enrichment Analysis (GSEA) identified nine significant pathways related to DR. Immune infiltration analysis indicated increased infiltration of fibroblasts and endothelial cells in DR patients. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADIPOQ gene expression as the disease progressed in our mouse models. At the protein level, ELISA results from sera of 31 patients and 11 control subjects demonstrated significantly lower adiponectin expression in the proliferative diabetic retinopathy (PDR) group compared to controls. Our findings reveal that adiponectin is involved in the advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) axis, as evidenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression. We combined bioinformatics analysis with scRNA-seq and ELISA. Finally, we proposed the hypothesis of a vicious cycle of DR, adiponectin and AGEs-RAGE axis. GEO: Gene Expression Omnibus, KEGG: Kyoto Encyclopedia of Genes and Genomes, GSEA: Gene Set Enrichment Analysis, scRNA-seq: Single-cell RNA sequencing, DR: Diabetic retinopathy, AGEs: Advanced glycation end products, RAGE: receptor of advanced glycation end products. [Display omitted] •ADIPOQ establishes a positive feedback loop related with AGEs-RAGE axis that acts as a central regulator of DR.•Fibroblasts and endothelial cells appeared to enhance infiltration in DR patient samples.•Stromal and basement membrane connective tissue deposition may be involved in the pathogenesis of DR.