Long noncoding ribonucleic acid ENST00000517482 enhances mesenchymal stem cell therapy against acute lung injury

Recent findings reveal that long non-coding RNA ENST00000517482 (ENST) protects mesenchymal stem cells (MSCs) from mitochondrial apoptosis via the microRNA-539/c-MYC axis, thereby enhancing their paracrine efficacy against lipopolysaccharide-induced acute lung injury (ALI) in vitro. Furthermore, ENST promotes autophagy through LC3B, autophagy related 7, and autophagy related 5, suggesting a dual role in MSC-mediated lung repair. However, translating these benefits to in vivo applications faces critical challenges. Autophagy, while protective in vitro, may exacerbate epithelial damage during ischemia-reperfusion or hyperoxic ALI if uncontrolled. Additionally, systemic MSC infusion suffers from poor pulmonary engraftment, limiting therapeutic efficiency. To overcome these barriers, future research should prioritize extracellular vehicle-based delivery of ENST-modified MSCs, combined with strategies to fine-tune autophagy via phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin or AMP-activated protein kinase/c-Jun-N-terminal kinase modulation. Rigorous validation in endotoxemia and ventilator-induced ALI models, with longitudinal assessment of autophagy and mitochondrial dynamics, will be essential to optimize this approach for clinical translation.