FGD5-AS1 and Th1/Th2 imbalance in the progression of diabetic nephropathy: evidence from bioinformatic and experimental validation

An imbalance of Th1/Th2 immune cells is a key contributor to the progression of inflammatory diabetic nephropathy (DN). Although our understanding of immune cell involvement in DN remains limited, this study aimed to investigate the expression and regulatory mechanisms of Th1/Th2-associated genes in PBMCs from diabetic patients. We included a total of 90 participants: 30 with type 2 diabetes mellitus (T2D) without nephropathy, 15 with microalbuminuria, 15 with end-stage renal disease (ESRD), and 30 healthy controls. Through analysis of the GSE43769 dataset and literature review, the lncRNA FGD5-AS1 was identified. The expression levels of TBX21 (Th1) and GATA3 (Th2) transcription factors, along with their respective cytokines, IFN-γ and IL-4, were measured using real-time PCR. Correlation analysis between gene expression and clinical parameters, including BUN, ESR, urea, GFR, FBS, creatinine, and HbA1C, was also evaluated. Significant upregulation of TBX21 and IFN-γ was identified among participants diagnosed with microalbuminuria and ESRD. Conversely, the expression of GATA3 and IL-4 progressively diminished across T2D, microalbuminuria, and ESRD groups in comparison to healthy subjects. Although FGD5-AS1 expression was reduced in T2D patients (not statistically significant), its expression increased significantly in patients with microalbuminuria and ESRD, suggesting dynamic regulation during disease progression. These findings highlight novel potential biomarkers and suggest that targeting inflammatory pathways could be explored as a precision medicine approach in DN.