CircNRIP1 KNOCKDOWN ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED HUMAN KIDNEY 2 CELL APOPTOSIS AND INFLAMMATION THROUGH...

Area of Science:

• Molecular Biology
• Cell Biology
• Renal Pathophysiology

Background:

• Sepsis-induced acute kidney injury (AKI) is a critical condition with limited therapeutic options.
• Circular RNAs (circRNAs) play regulatory roles in AKI, with circNRIP1 overexpressed in AKI patients' blood.
• The specific role of circNRIP1 in septic AKI pathogenesis remains largely unexplored.

Purpose of the Study:

• To investigate the role and mechanism of circNRIP1 in lipopolysaccharide (LPS)-induced septic acute kidney injury (AKI) in human kidney 2 (HK2) cells.
• To explore the regulatory pathway involving circNRIP1, miR-339-5p, and oxidative stress-responsive kinase 1 (OXSR1) in septic AKI.

Main Methods:

• Establishment of a septic AKI cell model using LPS stimulation of HK2 cells.
• Quantitative real-time polymerase chain reaction and Western blotting to assess expression levels of circNRIP1, miR-339-5p, OXSR1, and apoptosis-related proteins (Bcl2, Bax, cleaved-caspase 3).
• Cell viability assays (cell counting kit-8), apoptosis analysis (flow cytometry), and mechanistic assays to determine molecular interactions.

Main Results:

• CircNRIP1 was significantly upregulated in septic AKI patients' blood and LPS-treated HK2 cells.
• CircNRIP1 depletion reduced LPS-induced HK2 cell apoptosis and inflammation, while downregulating miR-339-5p.
• CircNRIP1 acts as a molecular sponge for miR-339-5p, leading to increased OXSR1 expression; OXSR1 overexpression reversed the protective effects of circNRIP1 knockdown.

Conclusions:

• CircNRIP1 exacerbates LPS-induced damage in HK2 cells, contributing to septic AKI.
• The circNRIP1/miR-339-5p/OXSR1 axis is a key pathway in the pathogenesis of septic AKI.
• Targeting circNRIP1 may represent a novel therapeutic strategy for managing sepsis-induced AKI.