Dissecting the role of SPRY4-IT1 and TUG1 in modulating miR-425/TGF-β/ Smad signaling in mediating renal fibrosis and inflammation in lupus nephritis: Novel biomarkers and therapeutic targets.

Lupus nephritis (LN), the severe complication of systemic lupus erythematosus (SLE), is driven by inflammation and fibrosis, often leading to chronic kidney diseases. The current study aimed to elucidate the roles of long non-coding RNAs (lncRNAs) SPRY4-IT1 and TUG1, and miR-425 in modulating the TGF-β/Smad signaling pathway and to assess their potential as biomarkers and therapeutic targets. A case-control study was conducted involving 100 participants, including LN patients (n = 35), SLE patients without LN (n = 35), and healthy controls (n = 30). Serum expression levels of SPRY4-IT1, TUG1, miR-425 and Smads were measured using qRT-PCR, while TGF-β, fibronectin,TNF-α and PIIINP were analyzed via ELISA. The results showed a significant upregulation of SPRY4-IT1 and TUG1 and a downregulation of miR-425 in LN patients compared to controls (p < 0.01). These ncRNAs demonstrated strong correlations with TGF-β, Smad2/3, and other fibrotic markers, while inversely correlating with miR-425. ROC curve analysis identified SPRY4-IT1 as the most robust diagnostic marker (AUC = 0.85, sensitivity = 82 %, specificity = 70 %). Pathway analyses confirmed their involvement in inflammatory and fibrotic processes. These findings suggest that SPRY4-IT1 and TUG1 contribute to LN pathogenesis through the miR-425/TGF-β/Smad axis, underscoring their potential as novel diagnostic and therapeutic targets. Further research in larger cohorts is warranted to validate these findings and explore clinical applications.