Serum albumin modified by carbamoylation impairs macrophage cholesterol efflux in diabetic kidney disease

Lira, Aécio Lopes de Araújo; Santana, Monique F. M.; Pinto, Raphael; Minanni, Carlos André; Iborra, Rodrigo Tallada; Lima, Adriana Machado Saldiba de; Côrrea-Giannella, Maria Lúcia; Passarelli, Marisa; Queiroz, Márcia Silva

doi:10.1016/j.jdiacomp.2021.107969

Cited by 5 publications

(4 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is suggested that albumin may be linked to the adipocytokine signaling pathway, consistent with the findings of this study's enrichment analysis. Albumin isolated from DN patients undergoes significant aminoacylation, which can hinder cholesterol efflux mediated by HDL2 and HDL3, leading to abnormal lipid accumulation [ 63 ]. In a state of disrupted blood glucose and lipid metabolism, filtered albumin exposes albumin-bound long-chain fatty acids on the surface of the proximal tubule.…”

Section: Discussionmentioning

confidence: 99%

Identification of Lipotoxicity-Related Biomarkers in Diabetic Nephropathy Based on Bioinformatic Analysis

Nie,

Yang,

Cheng

et al. 2024

Journal of Diabetes Research

View full text Add to dashboard Cite

Objective: This study is aimed at investigating diagnostic biomarkers associated with lipotoxicity and the molecular mechanisms underlying diabetic nephropathy (DN).Methods: The GSE96804 dataset from the Gene Expression Omnibus (GEO) database was utilized to identify differentially expressed genes (DEGs) in DN patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the DEGs. A protein–protein interaction (PPI) network was established to identify key genes linked to lipotoxicity in DN. Immune infiltration analysis was employed to identify immune cells with differential expression in DN and to assess the correlation between these immune cells and lipotoxicity-related hub genes. The findings were validated using the external dataset GSE104954. ROC analysis was performed to assess the diagnostic performance of the hub genes. The Gene set enrichment analysis (GSEA) enrichment method was utilized to analyze the key genes associated with lipotoxicity as mentioned above.Result: In this study, a total of 544 DEGs were identified. Among them, extracellular matrix (ECM), fatty acid metabolism, AGE-RAGE, and PI3K-Akt signaling pathways were significantly enriched. Combining the PPI network and lipotoxicity-related genes (LRGS), LUM and ALB were identified as lipotoxicity-related diagnostic biomarkers for DN. ROC analysis showed that the AUC values for LUM and ALB were 0.882 and 0.885, respectively. The AUC values for LUM and ALB validated in external datasets were 0.98 and 0.82, respectively. Immune infiltration analysis revealed significant changes in various immune cells during disease progression. Macrophages M2, mast cells activated, and neutrophils were significantly associated with all lipotoxicity-related hub genes. These key genes were enriched in fatty acid metabolism and extracellular matrix-related pathways.Conclusion: The identified lipotoxicity-related hub genes provide a deeper understanding of the development mechanisms of DN, potentially offering new theoretical foundations for the development of diagnostic biomarkers and therapeutic targets related to lipotoxicity in DN.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Lipotoxicity-Related Biomarkers in Diabetic Nephropathy Based on Bioinformatic Analysis

Nie,

Yang,

Cheng

et al. 2024

Journal of Diabetes Research

View full text Add to dashboard Cite

show abstract

“…Attenuated lymphoproliferation ameliorates diabetic nephropathy and high-fat diet-induced nephrolipotoxicity, suggesting a causal relationship between lipotoxicity and lymphoproliferation and a link to macrophages activation to DN ( 82 ). Carbamylated-modified serum albumin impairs macrophages cholesterol efflux in kidneys of T2DM, which results in renal damage by promoting lipid accumulation in macrophages and impairment of reverse cholesterol transport ( 83 ). Myeloid-associated protein 8 (MRP8 or S100A8) is elevated in glomeruli of T1DM and T2DM mice ( 84 ).…”

Section: Pathogenic Roles Of Macrophages In Dnmentioning

confidence: 99%

Roles and crosstalks of macrophages in diabetic nephropathy

You

Shao

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is the most common chronic kidney disease. Accumulation of glucose and metabolites activates resident macrophages in kidneys. Resident macrophages play diverse roles on diabetic kidney injuries by releasing cytokines/chemokines, recruiting peripheral monocytes/macrophages, enhancing renal cell injuries (podocytes, mesangial cells, endothelial cells and tubular epithelial cells), and macrophage-myofibroblast transition. The differentiation and cross-talks of macrophages ultimately result renal inflammation and fibrosis in DN. Emerging evidence shows that targeting macrophages by suppressing macrophage activation/transition, and macrophages-cell interactions may be a promising approach to attenuate DN. In the review, we summarized the diverse roles of macrophages and the cross-talks to other cells in DN, and highlighted the therapeutic potentials by targeting macrophages.

show abstract

“…Moreover, the effects of AGE-albumin in impairing cholesterol removal and inducing inflammation were sustained in cells even after the removal of AGE-albumin from the incubating medium, reflecting the long-lasting effects of advanced glycated albumin on macrophage lipid homeostasis derangements and inflammation [ 85 ]. Recent studies [ 98 , 99 ] demonstrate that albumin and HDLs isolated from patients with diabetes and chronic kidney disease, with decreased glomerular filtration, diminishes the efflux of cholesterol mediated by HDLs in macrophages, which may be a result of glycation and the carbamoylation that occurs in these patients with diabetes and CKD. Furthermore, hyperglycemia, by inducing ROS, promotes epigenetic changes that favor NF-KB activation and cholesterol efflux down-regulation [ 100 ].…”

Section: Sweet Ages Driving the Bitter Pathophysiology Of Cvdmentioning

confidence: 99%

Advanced Glycation End Products: A Sweet Flavor That Embitters Cardiovascular Disease

Pinto

Minanni

Lira

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Epidemiological studies demonstrate the role of early and intensive glycemic control in the prevention of micro and macrovascular disease in both type 1 and type 2 diabetes mellitus (DM). Hyperglycemia elicits several pathways related to the etiopathogenesis of cardiovascular disease (CVD), including the generation of advanced glycation end products (AGEs). In this review, we revisit the role played by AGEs in CVD based in clinical trials and experimental evidence. Mechanistic aspects concerning the recognition of AGEs by the advanced glycosylation end product-specific receptor (AGER) and its counterpart, the dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST) and soluble AGER are discussed. A special focus is offered to the AGE-elicited pathways that promote cholesterol accumulation in the arterial wall by enhanced oxidative stress, inflammation, endoplasmic reticulum stress and impairment in the reverse cholesterol transport (RCT).

show abstract

Serum albumin modified by carbamoylation impairs macrophage cholesterol efflux in diabetic kidney disease

Cited by 5 publications

References 29 publications

Identification of Lipotoxicity-Related Biomarkers in Diabetic Nephropathy Based on Bioinformatic Analysis

Identification of Lipotoxicity-Related Biomarkers in Diabetic Nephropathy Based on Bioinformatic Analysis

Roles and crosstalks of macrophages in diabetic nephropathy

Advanced Glycation End Products: A Sweet Flavor That Embitters Cardiovascular Disease

Contact Info

Product

Resources

About