Mechanism study of LncRNA PRINS targeting TFAM to regulate mitochondrial dysfunction in human renal tubular...

Acute kidney injury (AKI) is a significant clinical problem associated with high morbidity and mortality. The psoriasis susceptibility-associated RNA gene (PRINS) is a stress-induced transcript implicated in kidney disease. However, its role in regulating mitochondrial function during AKI remains unclear.

We measured the expression of LncRNA PRINS and key mitochondrial genes, including mitochondrial transcription factor A (TFAM), NDUFV1, NDUFS1, and CYPD, in peripheral blood and renal tissues from AKI patients and controls. A hypoxia/reoxygenation (H/R) model was established in HK-2 cells. Following LncRNA PRINS knockdown, we assessed cell proliferation, apoptosis, mitochondrial function (mPTP opening, membrane potential, ROS levels, complex I activity), and mitochondrial morphology via electron microscopy. Expression changes of related genes were measured. Subsequently, TFAM-the gene with the most pronounced expression change-was knocked down under H/R, and the cellular phenotypes, mitochondrial function, and gene expressions were re-evaluated.

The expression of LncRNA PRINS was significantly upregulated in both AKI patients and H/R-induced HK-2 cells. LncRNA PRINS inhibition alleviated H/R-induced suppression of cell proliferation, reduced apoptosis, partially reversed mitochondrial dysfunction, and corrected the aberrant expression of functional genes. Further analysis identified TFAM as a downstream target of LncRNA PRINS.LncRNA PRINS knockdown restored TFAM expression suppressed by H/R, whereas TFAM knockdown attenuated the protective effects mediated by LncRNA PRINS silencing.

LncRNA PRINS may contribute to mitochondrial dysfunction, dysregulation of key genes, and cellular damage in AKI by negatively regulating TFAM expression. Targeting LncRNA PRINS could thus represent a novel therapeutic strategy for the prevention and treatment of AKI.