Full
Outline
To identify oxidative stress (OS)- and immune-related biomarkers and their therapeutic targets in diabetic nephropathy (DN). The development of DN is closely associated with chronic inflammation, which exhibits complex interactions between OS and immune-metabolic alterations, collectively driving disease progression.
Download the GSE142153 dataset and evaluate immune cell infiltration in its samples. Simultaneously perform differential analysis on this dataset, intersecting the resulting differentially expressed genes (DEGs) with overall survival-related genes (OSRGs) to identify OS-related differentially expressed genes (DE-OSRGs) in the DN process. Functional enrichment analysis clarified the biological roles of DE-OSRGs. A protein-protein interaction (PPI) network was constructed, and core DE-OSRGs were selected using the MCC algorithm in the cytoHubba plugin. After validating their reliability via ROC diagnostic curves, target miRNAs of DE-OSRGs were cross-analyzed with DN-related microRNAs to identify miR-150-5p, with binding sites subsequently validated. Finally, the expression of core DE-OSRGs and the mechanism of action of their target miRNAs were validated using a rat DN model.
Bioinformatics analysis identified TLR7 as the core DE-OSRG, and combined with target miRNA prediction, miR-150-5p was determined as the primary focus of this study. Animal experiments demonstrated that miR-150-5p agomir significantly downregulated TLR7 and NF-κB p65 expression (P<0.05), reduced the production of malondialdehyde (MDA), a marker of oxidative stress (P<0.05), and increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) (P<0.05). Furthermore, miR-150-5p suppressed secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) (P<0.05), mitigated immune cell infiltration, and improved renal pathological damage.
By down-regulating TLR7 and modulating the NF-κB pathway, miR-150-5p attenuates OS injury and inflammation in DN, thereby improving renal function and offering a promising therapeutic target.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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