• Fndc5 overexpression enhances MSC retention in injured lungs and augments their proliferation and migration in vitro.
• MSCs-Fndc5 treatment attenuates lung inflammation, reduces pulmonary edema and fibrosis, and preserves vascular integrity in sepsis-induced ALI/ARDS.
• The protective effects of MSCs-Fndc5 are mediated via activation of the PI3K/AKT signaling pathway in endothelial cells.
• Fndc5-modified MSCs represent a promising therapeutic strategy for sepsis-induced ALI/ARDS.