Hydrogen Repairs LPS-Induced Endothelial Progenitor Cells Injury via PI3K/AKT/eNOS Pathway

Area of Science:

• Biomedical Science
• Cell Biology
• Pulmonary Medicine

Background:

• Endotoxins like lipopolysaccharide (LPS) can damage endothelial cells (ECs) and impair endothelial progenitor cells (EPCs), compromising lung integrity and vascular repair.
• EPCs are crucial for vascular repair, migrating to damaged sites and differentiating into ECs to restore endothelial barrier function.
• Hydrogen (H2) has shown potential in repairing lung injury and EC damage, suggesting a possible protective role for EPCs.

Purpose of the Study:

• To investigate whether H2 protects EPCs against LPS-induced damage.
• To elucidate the underlying molecular mechanism of H2's protective effects on EPCs.

Main Methods:

• Established an LPS-induced EPC damage model using bone marrow-derived EPCs from ICR mice.
• Treated damaged EPCs with H2, and utilized PI3K inhibitor LY294002 and eNOS inhibitor L-NAME.
• Assessed EPC proliferation, migration, and angiogenesis using MTT, Transwell, and tube formation assays.
• Analyzed protein expression levels of p-AKT, eNOS, and p-eNOS via Western blot.

Main Results:

• H2 significantly repaired EPC proliferation, migration, and tube formation functions impaired by LPS.
• Inhibition of PI3K/AKT (LY294002) or eNOS (L-NAME) attenuated H2's protective effects on LPS-induced EPC dysfunction.
• H2 restored LPS-suppressed levels of p-AKT, eNOS, and p-eNOS, with inhibitors blocking these increases.

Conclusions:

• H2 protects EPCs from LPS-induced damage, preserving their proliferative, migratory, and angiogenic capacities.
• The protective mechanism of H2 involves the activation of the PI3K/AKT/eNOS signaling pathway.
• H2 demonstrates therapeutic potential for lung injury by safeguarding EPC function via this pathway.