Genistein promotes M1 macrophage apoptosis and reduces inflammatory response by disrupting miR-21/TIPE2 pathway

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Epigenetics

Background:

• Cardiovascular diseases are a leading cause of mortality, with vascular injury linked to macrophage apoptosis and inflammation.
• Genistein, a phytoestrogen, shows cardiovascular benefits, but its mechanisms require elucidation.
• Understanding genistein's role in regulating macrophage response is crucial for cardiovascular disease treatment.

Purpose of the Study:

• To investigate the mechanism by which genistein modulates apoptosis and inflammation in lipopolysaccharide (LPS)-stimulated macrophages.
• To determine genistein's efficacy in an LPS-induced cardiovascular injury mouse model.
• To elucidate the role of the miR-21/TIPE2 pathway in genistein's protective effects.

Main Methods:

• RAW264.7 cells were treated with genistein, LPS, NF-κB inhibitor, and AKT agonist.
• C57BL/6 mice fed a high-fat diet were administered genistein.
• miR-21 expression, TIPE2 levels, NF-κB activity, and AKT phosphorylation were analyzed.

Main Results:

• LPS increased macrophage apoptosis resistance and inflammation by upregulating miR-21, which downregulated TIPE2.
• Genistein reduced miR-21 expression by inhibiting NF-κB, subsequently blocking the TLR4 pathway and AKT phosphorylation via TIPE2.
• Genistein treatment inhibited LPS-induced cardiovascular injury in mice.

Conclusions:

• The miR-21/TIPE2 pathway is implicated in M1 macrophage apoptosis and inflammation.
• Genistein exerts epigenetic control over LPS-induced cardiovascular injury by regulating the Vmp1 promoter via NF-κB.
• Genistein represents a potential therapeutic agent for cardiovascular diseases by targeting the miR-21/TIPE2 pathway.