Common gene signatures and molecular mechanisms of diabetic nephropathy and metabolic syndrome

Abstract

Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Multiple metabolic toxicities, redox stress, and endothelial dysfunction contribute to the development of diabetic glomerulosclerosis and DN. Metabolic syndrome (MetS) is a pathological state in which the body's ability to process carbohydrates, fats, and proteins is compromised because of metabolic disorders, resulting in redox stress and renal remodeling. However, a causal relationship between MetS and DN has not been proven. This study aimed to provide valuable information for the clinical diagnosis and treatment of MetS with DN.

Methods: Here, transcriptome data of DN and MetS patients were obtained from the Gene Expression Omnibus database, and seven potential biomarkers were screened using bioinformatics analysis. In addition, the relationship between these marker genes and metabolism and immune infiltration was explored. Among the identified marker genes, the relationship between PLEKHA1 and the cellular process, oxidative phosphorylation (OXPHOS), in DN was further investigated through single-cell analysis.

Results: We found that PLEKHA1 may represent an important biomarker that perhaps initiates DN by activating B cells, proximal tubular cells, distal tubular cells, macrophages, and endothelial cells, thereby inducing OXPHOS in renal monocytes.

Conclusion: Overall, our findings can aid in further investigation of the effects of drug treatment on single cells of patients with diabetes to validate PLEKHA1 as a therapeutic target and to inform the development of targeted therapies.

Keywords: diabetic nephropathy; oxidative phosphorylation; single-cell analysis; transcription data; type 2 diabetes.