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...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.展开更多
文摘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.
