Exploring the interplay between adipokine-mediated celastrol target genes and T cells in diabetic nephropathy: a mendelian randomization-based causal inference

Diabetology & Metabolic Syndrome, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 18, 2025

Diabetic nephropathy (DN) is influenced by dysregulated adipokines, which play a key role in inflammation, immune responses, and lipid metabolism. However, the precise molecular mechanisms linking adipokine dysregulation, cell infiltration, metabolic reprogramming DN remain poorly understood. Celastrol, bioactive regulator, has been shown to mitigate renal immune-inflammatory damage inhibiting PI3K/Akt/NF-κB signaling pathway. Yet, its specific impact on adipokine-mediated responses metabolism unclear. This study aims elucidate interplay between target genes investigate how celastrol modulates these interactions. Gene expression profiles of patients were obtained from GEO datasets (GSE30122 GSE30528) analyzed for differentially expressed (DEGs) using limma package. set variation analysis (GSVA) was conducted assess pathways, while Mendelian randomization (MR) Pearson correlation evaluated association DEGs adipokines. Immune infiltration IOBR R package (MCP-counter xCell methods), followed MR DN-related responses. Celastrol identified SEA database. A total 70 intersecting identified. GSVA revealed that brown beige adipocyte differentiation pathways downregulated, adipocyte-related upregulated (p < 0.05). demonstrated adiponectin negatively associated with (OR = 0.77, P 0.005), whereas leptin 1.92, 0.016) resistin 1.43, 0.001) positively associated. Three genes, MAGI2, FGF9, THBS2 linked risk T infiltration. correlated 0.51, 6.7e-06), FGF9 -0.8, 2.2e-16) MAGI2 0.75, 1.3e-13) correlated. 22 including THBS2, Our findings reveal progression through adipokine-immune crosstalk, emerging as regulatory genes. These insights provide new avenues biomarker discovery therapeutic implications development DN.

Language: Английский

Identification of genes related to fatty acid metabolism in type 2 diabetes mellitus

Biochemistry and Biophysics Reports, Journal Year: 2024, Volume and Issue: 40, P. 101849 - 101849

Published: Oct. 22, 2024

Language: Английский