Photo Credit: Kateryna
The following is a summary of “GPX4 expression changes in proximal tubule cells highlight the role of ferroptosis in IgAN,” published in the January 2025 issue of Scientific Reports by Qing et al.
Oxidative stress (OS) contributes to renal injury, fibrosis, and rapid failure. Its role in IgA nephropathy, a key driver of chronic kidney disease, remains unclear.
Researchers conducted a retrospective study to examine OS in IgA nephropathy and its role in cell and tissue injury
They collected and analyzed Single-cell RNA sequencing (scRNA-seq) and microarray data of IgAN. They conducted gene set variation analysis (GSVA) to identify OS pathway alterations in proximal tubule cells (PTCs) and performed enrichment analysis on differentially expressed OS-related genes, focusing on ferroptosis. They collected ferroptosis regulators to define ferroptosis activity in PTCs and verified GPX4 expression in IgAN kidney tissues using immunohistochemistry. They used GSVA of microarray data to assess ferroptosis activity in the tubulointerstitium.
The results showed significant alterations in OS pathways in PTCs of patients with IgAN. Differentially expressed OS-related genes were linked to ferroptosis, with a notable increase in ferroptosis suppression. GPX4 expression in PTCs was highly significant and confirmed by immunohistochemistry. GSVA of microarray data showed decreased ferroptosis activity in the tubulointerstitium, with stronger ferroptosis inhibition.
Investigators demonstrated that ferroptosis inhibition could help reduce OS injury in IgAN. GPX4 was a specific marker for PTCs and a potential therapeutic target.
Source: nature.com/articles/s41598-025-87228-9
