RRM2 attenuates renal tubular ferroptosis in diabetic kidney disease via the PI3K/Akt/Nrf2 pathway: Strengths, limitations, and future research directions.

Diabetic kidney disease (DKD) has become the primary cause of end-stage renal disease. However, its pathological mechanism remains incompletely understood. Ribonucleotide reductase M2 (RRM2) is a small subunit of ribonucleotide reductases, which is involved in nucleotide metabolism and catalyzes the conversion of nucleotides to deoxynucleotides, thereby maintaining the deoxyribonucleoside triphosphate pools required for DNA biosynthesis, repair, and replication. This study establishes a novel connection between the enzyme RRM2-traditionally recognized for its role in DNA synthesis-and the pathological progression of DKD, thereby filling the gap in identifying the "bridge molecule" between ferroptosis and the PI3K/Akt/Nrf2 pathway.