LncRNA PVT1 accelerates LPS-induced septic acute kidney injury through targeting miR-17-5p and regulating NF-κB pathway.

Abstract

BACKGROUND:

Long noncoding RNA PVT1 is associated with diverse human diseases, including acute kidney injury (AKI). However, our understandings of PVT1 on septic AKI are limited.

METHODS:

The septic AKI model was constructed through lipopolysaccharide (LPS) treatment. PVT1 and miR-17-5p levels were measured using qRT-PCR analysis. The concentrations of inflammatory cytokines were determined with ELISA kits. Cell viability and apoptosis were assessed using CCK-8 assay and flow-cytometric analysis, respectively. Protein levels were examined using western blot assay. The targeting association between miR-17-5p and PVT1 was verified by dual-luciferase reporter, RIP and RNA pull-down assays.

RESULTS:

PVT1 level was elevated and miR-17-5p level was declined in septic AKI patients' serum and LPS-stimulated HK-2 cells. Cell viability was suppressed and cell apoptosis and inflammation were promoted after LPS treatment. PVT1 knockdown or miR-17-5p elevation restored LPS-mediated HK-2 cell injury. MiR-17-5p was sponged by PVT1, and its inhibition weakened the impact of PVT1 deficiency on LPS-mediated injury of HK-2 cells. In addition, PVT1 knockdown inactivated NF-κB pathway mediated by LPS treatment, but miR-17-5p inhibition further reversed this effect.

CONCLUSION:

PVT1 knockdown promoted cell viability, suppressed inflammatory response and apoptosis by regulating miR-17-5p expression and NF-κB pathway in LPS-stimulated HK-2 cells.

• Authors: Wensheng Yuan, Xiaoqing Xiong, Jinlong Du, Qi Fan, Rong Wang, Xia Zhang
• Journal: International urology and nephrology (Int Urol Nephrol) Vol. 53 Issue 11 Pg. 2409-2419 (Nov 2021) ISSN: 1573-2584 [Electronic] Netherlands
• PMID: 34089461 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• MIRN17 microRNA, human
• MicroRNAs
• NF-kappa B
• PVT1 long-non-coding RNA, human
• RNA, Long Noncoding

Topics

• Acute Kidney Injury (etiology)
• Cells, Cultured
• Humans
• MicroRNAs (physiology)
• NF-kappa B (physiology)
• RNA, Long Noncoding (physiology)
• Sepsis (etiology)
• Signal Transduction (physiology)
• Time Factors