The Positive Feedback Regulation of NF-κB/miR-21c/IL-9 Axis in Septic Acute Kidney Injury

Area of Science:

• Nephrology
• Molecular Biology
• Immunology

Background:

• Sepsis-associated acute kidney injury (septic AKI) is a major cause of death in critically ill patients.
• Current treatments for septic AKI are limited due to poor understanding of the underlying molecular mechanisms.
• Renal inflammation and tubular damage are key pathological features of septic AKI.

Purpose of the Study:

• To elucidate the molecular mechanisms driving renal inflammation and injury in septic AKI.
• To identify potential therapeutic targets for mitigating kidney damage in septic AKI.

Main Methods:

• Utilized a murine model of LPS-induced septic AKI and cultured proximal tubular cells.
• Investigated the role of miR-21c and its regulation by NF-κB.
• Assessed the interaction between miR-21c and interleukin-9 (IL-9) using molecular biology techniques.
• Evaluated the effects of modulating miR-21c and IL-9 on kidney function and injury markers.

Main Results:

• miR-21c was upregulated in septic AKI kidneys, driven by NF-κB activation.
• Inhibition of miR-21c attenuated kidney injury, reduced inflammation, and decreased tubular apoptosis.
• miR-21c directly targeted IL-9, and IL-9 restoration suppressed LPS-induced injury.
• IL-9 overexpression inhibited NF-κB p65 phosphorylation, suggesting a feedback loop.

Conclusions:

• Identified a pathogenic NF-κB/miR-21c/IL-9 feedback loop that exacerbates septic AKI.
• Targeting miR-21c or enhancing IL-9 signaling presents promising therapeutic strategies for septic AKI.
• This discovery could lead to improved treatment outcomes for patients with septic AKI.