Abstract: TH-PO284

Indirect Therapeutic Role of Immunosuppressive Micro-RNA for Sepsis Induced AKI via Spleen

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Author

  • Funahashi, Yoshio, Nagoya University, Nagoya,AICHI, Japan
Background

Sepsis is life-threatening organ dysfunction caused by dysregulated immune response to infection. It is known that sepsis with acute kidney injury (AKI) shows high mortality rate. However, therapies to treat sepsis and AKI are largely ineffective because of its pathophysiological complexity. Several studies have reported that some micro-RNAs (miRNAs) acted as a regulator of systemic inflammation. Here, we revealed the significance of spleen to regulate septic state by induction of immunosuppressive miRNA.

Methods

In vitro study, miR-X, which targeting toll like receptor/NF-kB pathway, was transfected into RAW264.7 cells. After transfection, cells were treated with lipopolysaccharide (LPS) for 6h, then RNA, protein, and supernatant were purified. In vivo study, 8-12 week-old C57BL/6 male mice, with or without splenectomy, were treated with miR-X expression plasmid combined with polyethyleneimine (PEI), 7 days before sepsis. Sepsis was induced by cecal ligation and puncture (CLP). Organs were harvested at 24h after CLP.

Results

In vitro study, miR-X transfected cells were tolerant toward LPS stimulation, and showed low NF-kB activity. In vivo study, miR-X expression plasmid/PEI complex was mainly detected in splenic macrophages. miR-X plasmid group showed the improvement of survival rate, inflammatory cytokine production, renal dysfunction, and renal tubular damage. In addition, less apoptotic cells were observed in spleen of miR-X expression plasmid group, than that of empty plasmid group. Interestingly, anti-inflammatory effect of miR-X was rarely observed in splenectomized mice.

Conclusion

Splenic induction of miR-X prevented dysregulated systemic inflammation in sepsis and attenuated AKI. In addition, we provided the new treatment strategy for sepsis induced AKI by targeting spleen with specific miRNA.