Peroxiredoxin 6 overexpression attenuates lipopolysaccharide-induced acute kidney injury

Area of Science:

• Biochemistry
• Cell Biology
• Pathology

Background:

• Peroxiredoxin 6 (PRDX6) is an antioxidant enzyme linked to inflammatory responses.
• Acute kidney injury (AKI) can be triggered by lipopolysaccharide (LPS), a potent inflammatory agent.
• Understanding PRDX6's role in LPS-induced AKI is crucial for potential therapeutic interventions.

Purpose of the Study:

• To investigate the protective role of Peroxiredoxin 6 (PRDX6) in lipopolysaccharide (LPS)-induced acute kidney injury (AKI).
• To elucidate the underlying mechanisms by which PRDX6 influences oxidative stress, inflammation, and apoptosis in AKI.

Main Methods:

• Utilized PRDX6-overexpressing transgenic mice and wild-type littermates subjected to LPS-induced AKI.
• Assessed mortality, renal injury, inflammatory cell infiltration, and apoptosis.
• Measured reactive oxygen species (ROS) levels and activation of p38 MAPK and JNK signaling pathways in kidney tissues.
• Examined the effects of PRDX6 inhibition and hydrogen peroxide in primary renal proximal tubular cells.

Main Results:

• PRDX6-overexpressing mice exhibited significantly reduced mortality and kidney damage compared to wild-type mice following LPS challenge.
• LPS-induced infiltration of macrophages, T-cells, and neutrophils, along with apoptotic cell counts, were decreased in PRDX6 mice.
• PRDX6 overexpression attenuated LPS-induced oxidative stress, p38 MAPK, and JNK activation in the kidneys.
• The protective effects of PRDX6 were reversed by a PRDX6 inhibitor or hydrogen peroxide treatment in renal cells.

Conclusions:

• PRDX6 overexpression confers protection against LPS-induced acute kidney injury.
• This protection is mediated by the suppression of ROS production, leading to the inactivation of p38 MAPK and JNK pathways.
• PRDX6 mitigates renal apoptosis and leukocyte infiltration, highlighting its therapeutic potential in AKI.