The RNA binding protein hnRNPK protects against adriamycin-induced podocyte injury

Podocytes maintain the integrity of the glomerular filtration barrier and serve as the final barrier to protein loss. Podocyte injury may induce severe apoptosis, which can result in serious kidney damage and disease. Therefore, it is necessary to explore how podocyte injury can be prevented and to thereby discover a feasible therapy for kidney disease. However, the mechanism of podocyte injury is still unclear.

ADR-induced podocyte injury is ameliorated by hnRNPK both in vivo and in vitro. This observation provides a basis for a feasible therapy to prevent podocyte injury and subsequent kidney disease.

The mRNA and protein expression levels of synaptopodin and nephrin in MPC5 podocytes with adriamycin (ADR)-induced injury were detected by quantitative real-time PCR and western blot. The expression levels of heterogeneous nucleotide protein K (hnRNPK), caspase-3, Bax, and Bcl-2 protein in cells and tissues were measured using western blot. Proliferation were measured in treated MPC5 podocytes by Cell Counting Kit-8 (CCK-8) assay, EdU assay, and apoptosis was measured by Hoechst 32258 staining. Mitochondrial membrane potential disruption, lactate dehydrogenase (LDH) leakage, and reactive oxygen species (ROS) generation were measured using JC-1 staining, an LDH reagent kit, and a ROS detection kit. Hematoxylin and eosin (HE) staining was used to observe histological changes in mouse tissues.

Synaptopodin and nephrin were downregulated in ADR-treated podocytes. Overexpression of hnRNPK ameliorated the inhibitive effect of ADR treatment on podocyte proliferation and reduced its promotion of podocyte apoptosis. LDH leakage and ROS generation were increased in ADR-treated podocytes, but were reduced by hnRNPK treatment. Conclusions: ADR-induced podocyte injury is ameliorated by hnRNPK both in vivo and in vitro. This observation provides a basis for a feasible therapy to prevent podocyte injury and subsequent kidney disease.