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Abstract: FR-OR05

The Long Noncoding RNA GSTM3P1 Is Induced to Exacerbate Ischemic AKI by Antagonizing MicroRNA-668

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Wei, Qingqing, Augusta University Medical College of Georgia, Augusta, Georgia, United States
  • Zhou, Jiliang, Augusta University Medical College of Georgia, Augusta, Georgia, United States
  • Dong, Zheng, Augusta University Medical College of Georgia, Augusta, Georgia, United States

Long non-coding RNAs (lncRNAs) are a group of epigenetic regulators that may play important roles in kidney diseases, but the specific LncRNAs involved and the underlying mechanisms are poorly understood. We recently unveiled miR-668 as a potent protective microRNA in ischemic AKI (Wei Q et al. J Clin Invest 128:5448, 2018). By deep sequencing of mir-668-induced silencing complex, we have identified GSTM3P1, a lncRNA, as a potential interactor and regulator of mir-668.


The expression of GSTM3P1 and its mouse homologue gstm2-ps1 were examined in hypoxia-treated HK2 cells and in mouse kidneys after ischemic AKI. GSTM3P1 was overexpressed in renal cells for functional examination. Proximal tubule-specific gstm2-ps1 knockout mouse model was established to test its role in ischemic AKI in vivo.


GSTM3P1/gstm2-ps1 was markedly induced in the early phase of ischemic AKI models both in vitro and in vivo. In HK2 cells, qPCR indicated a significant increase of GSTM3P1 at 3 hours after 1% O2 treatment. In C57BL/6 mice, gstm2-ps1 was significantly induced in kidneys after 30 minutes of ischemia and 3 hours of reperfusion, which was also accompanied with the suppression of mir-668. In vitro, overexpression of GSTM3P1 led to more renal proximal tubular cell death after ATP depletion. GSTM3P1 overexpression in HEK cells caused significant decrease of the mature form of mir-668. A mir-668 binding site in GSTM3P1 was also confirmed by luciferase assay. We further generated kidney proximal tubule-specific gstm2-ps1 knockout (KO) mouse model. Compared to wild type littermates (WT), the conditional gstm2-ps1 KO mice were significantly protected from renal ischemia-reperfusion injury. Both blood urea nitrogen level [268.18±47.97 mg/dL (WT) vs 174.42±28.65 mg/dL (KO)] and the serum creatinine level [2.45±0.36 mg/dL (WT) vs 1.41±0.27 mg/dL (KO)] were remarkably decreased. Consistently, renal tubular damage and apoptosis were significantly suppressed in KO kidneys. KO kidneys also had lower tubular NGAL.


These results indicate that GSTM3P1/gstm2-ps1 is induced in ischemic AKI, and following induction it mediates tubular cell injury and death by interacting and antagonizing mir-668.


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