Dandelion exosome-like nanovesicles alleviate sepsis-induced acute kidney injury via SLC7A11-regulated ferroptosis

Sepsis is a systemic inflammatory response syndrome triggered by infection, resulting in organ dysfunction. Sepsis-induced acute kidney injury (S-AKI) is one of the most prevalent potential complications. Accumulating studies found that ferroptosis plays an important role in S-AKI. However, the specific regulatory mechanism is not clear. In the present study, we isolated plant-derived exosome-like nanovesicles (PELNs, named PGY-Exo herein) from Dandelion (Taraxacum Genus) and established an in vivo S-AKI model. Human umbilical vein endothelial cells (HUVECs) were stimulated with lipopolysaccharide (LPS) to mimic an in vitro septic injury model for evaluating the therapeutic effects of PGY-Exo. Proteomics was used to reveal the molecular mechanism by which PGY-Exo ameliorate AKI. In this study, PKH26-labeled PGY-Exo were confirmed to be taken up by HUVECs and renal tissues. PGY-Exo treatment alleviated S-AKI by suppressing the accumulation of reactive oxygen species (ROS) and multiple inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Proteomic screening found that solute carrier family 7 member 11 (SLC7A11) was the key downstream target of PGY-Exo. Downregulation of SLC7A11 abrogated the protective effects of PGY-Exo against LPS-induced HUVEC injury and dysfunction. Taken together, this study found that treatment with dandelion-derived exosome-like nanovesicles alleviated sepsis-induced ferroptosis and renal injury by upregulating SLC7A11 expression.