Formononetin Alleviates Ischemic Acute Kidney Injury by Regulating Macrophage Polarization through KLF6/STAT3 Pathway

Area of Science:

• Nephrology
• Immunology
• Pharmacology

Background:

• Formononetin exhibits anti-inflammatory properties in various diseases.
• The effect of formononetin on sterile inflammation in acute kidney injury (AKI) is not well understood.

Purpose of the Study:

• To investigate the protective effects of formononetin on ischemia/reperfusion-induced AKI (IRI-AKI).
• To explore the underlying anti-inflammatory mechanisms of formononetin in AKI, focusing on macrophage polarization and the KLF6/STAT3 pathway.

Main Methods:

• Utilized an IRI-AKI mouse model and bone marrow-derived macrophages (BMDMs).
• Assessed kidney function via serum creatinine and blood urea nitrogen levels.
• Analyzed kidney pathology, tubular injury markers (KIM-1, NGAL), pro-inflammatory cytokines, and macrophage infiltration.
• Conducted in vitro studies on macrophage polarization and investigated the KLF6/STAT3 pathway.

Main Results:

• Formononetin treatment significantly preserved kidney function and reduced renal tubular injury in IRI-AKI mice.
• Formononetin suppressed pro-inflammatory cytokine expression (MCP-1, TNF-α, IL-1β) and decreased macrophage infiltration.
• In vitro, formononetin inhibited LPS/IFN-γ-induced pro-inflammatory macrophage polarization, linked to KLF6/STAT3 pathway modulation.

Conclusions:

• Formononetin demonstrates significant renoprotective and anti-inflammatory effects in IRI-AKI.
• The mechanism involves the inhibition of KLF6/STAT3-mediated pro-inflammatory macrophage polarization.
• Formononetin represents a promising therapeutic candidate for treating IRI-AKI.