Cellular signalling · 2026
Mechanism study of LncRNA PRINS targeting TFAM to regulate mitochondrial dysfunction in human renal tubular epithelial cells under ischemia-reperfusion.
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Huang Xuan, Xue Songmin, Wulasihan Muhuyati, Chu Xueqian, Chen Sisi, Adeli Wulaer, Yernaer Tamasha, Tuohetiyaer Zulibiya, Nurelibieke Mulidure, Li Suhua, Lu Chen
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.